2024-03-28T09:09:31Zhttp://uobrep.openrepository.com/oai/requestoai:uobrep.openrepository.com:10547/2245442018-06-29T11:32:52Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
author
Bosslet, Klaus
author
Lee, Cindy
author
Richardson, Deborah
author
Orchard, Kim H.
department
University of Bedfordshire
2012-05-18T08:53:08Z
2011-12
Guinn, B.A. et al (2011) 'Expression of CD66 in non-Hodgkin lymphomas and multiple myeloma'. Eur. J. Haematol. 87 (6):554-5
1600-0609
21883478
10.1111/j.1600-0609.2011.01698.x
http://hdl.handle.net/10547/224544
European journal of haematology
en
non-hodgkins lymphoma
multiple myeloma
CD66
Expression of CD66 in non-Hodgkin lymphomas and multiple myeloma.
Article
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oai:uobrep.openrepository.com:10547/2245252018-06-29T11:31:44Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Lee, Cindy
author
Guinn, Barbara-Ann
author
Brooks, Suzanne E.
author
Richardson, Deborah
author
Orchard, Kim H.
2012-05-18T08:52:25Z
2010-06
Lee, C., Guinn, B.A., Brooks, S.E., Orchard, K. (2010) 'CD66a (CEACAM1) is the only CD66 variant expressed on the surface of plasma cells in multiple myeloma: a refined target for radiotherapy trials?' 149 (5):795-6
1365-2141
20230402
10.1111/j.1365-2141.2010.08100.x
http://hdl.handle.net/10547/224525
British journal of haematology
en
CD66
targetted radiotherapy
multiple myeloma
CD66a (CEACAM1) is the only CD66 variant expressed on the surface of plasma cells in multiple myeloma: a refined target for radiotherapy trials?
Article
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oai:uobrep.openrepository.com:10547/2245572020-04-23T07:34:59Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Cheuk, Adam T.C.
author
Wells, James W.
author
Chan, Lucas
author
Westwood, Nigel B.
author
Berger, Stuart A.
author
Yagita, Hideo
author
Okumura, Ko
author
Farzaneh, Farzin
author
Mufti, Ghulam J.
author
Guinn, Barbara-Ann
department
King's College London
2012-05-18T10:43:42Z
2009-03
Cheuk, A.T.C., Wells, J.W., Chan, L., Westwood, N.B., Berger, S.A., Yagita, H., Okumura, K., Farzaneh, F., Mufti, G.J., Guinn, B.A. (2009) 'Anti-tumor immunity in a model of acute myeloid leukemia', Leukemia and Lymphoma, 50 (3) , pp.447-54.
1029-2403
19197726
10.1080/10428190802653776
http://hdl.handle.net/10547/224557
Leukemia & lymphoma
Whole-cell vaccines allow the induction of anti-tumor immune responses without the need to define tumor antigens. We wished to directly compare, for the first time, the capacity of B7-1, B7-2 and 4-1BB ligand (4-1BBL) costimulatory molecules to convert murine and human acute myeloid leukemia (AML) cells into whole vaccines. 32Dc-kit is a murine myeloid cell line, which develops an AML-like disease over a protracted period, emulating human AML disease development. 32Dc-kit cells were modified to express elevated levels of B7-1, B7-2 or 4-1BBL, and each led to tumor rejection, although only mice injected with 32Dc-kit/B7-2 cells were able to reject subsequent parental tumor cell challenge. T-cell deficient nude mice were able to reject the 32Dc-kit variants, but they could not reject parental cell challenge; however, we found no evidence of cytotoxic T lymphocyte or natural killer (NK) activity ex vivo suggesting that tumor cell killing was mediated by an immune response that could not be recapitulated using purified NK or T cells as lone effectors. In human allogeneic mixed lymphocyte reactions (MLRs), we found no single costimulatory molecule was more effective, suggesting that the induction of a universal anti-tumor response will require a combination of costimulatory molecules.
en
whole cell vaccine
acute myeloid leukaemia
4-1BB ligand
co-stimulatory molecules
Anti-tumor immunity in a model of acute myeloid leukemia
Article
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oai:uobrep.openrepository.com:10547/2245532020-04-23T07:35:00Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
author
Mulherkar, R.
department
King's College London
2012-05-18T10:36:52Z
2008-12
Guinn, B.A., Mulherkar, R. (2008) 'International progress in cancer gene therapy' Cancer Gene Therapy 15 (12):765-75
1476-5500
18846114
10.1038/cgt.2008.66
http://hdl.handle.net/10547/224553
Cancer gene therapy
We overview the current status and most recent developments in the field of cancer gene therapy from an international viewpoint. We have largely based our review on presentations from the eighth annual meeting of the International Society for Cell and Gene Therapy of Cancer held in Mumbai, India (http://www.iscgt.com and http://www.iscgtindia.com). This has afforded us with the opportunity to describe the most recently published and unpublished data in the field of cancer gene therapy, gaining an insight into the priorities in this field today. In doing so, we hope to have provided a state of the art review of cancer gene therapy, with the help of some of the best-known researchers in the field. In addition, due to the location of the meeting, we had a unique opportunity to listen to some of the seminal cancer gene therapy work being performed in India at this time.
en
cancer gene therapy
international
International progress in cancer gene therapy
Article
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oai:uobrep.openrepository.com:10547/2245762020-04-23T07:35:09Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Collins, Sara A.
author
Guinn, Barbara-Ann
author
Harrison, Patrick T.
author
Scallan, Martina F.
author
O'Sullivan, Gerald C.
author
Tangney, Mark
department
Mercy University Hospital, Cork
department
University College Cork
2012-05-18T10:32:00Z
2008-04
Collins, S.A., Guinn, B.A., Harrison, P.T., Scallan, M.F., O'Sullivan, G.C., Tangney, M. (2008) 'Viral vectors in cancer immunotherapy: which vector for which strategy?' Current gene therapy 8 (2):66-78
1566-5232
18393828
http://hdl.handle.net/10547/224576
Current gene therapy
Gene therapy involves the transfer of genetic information to a target cell to facilitate the production of therapeutic proteins and is now a realistic prospect as a cancer treatment. Gene transfer may be achieved through the use of both viral and non-viral delivery methods and the role of this method in the gene therapy of cancer has been demonstrated. Viruses represent an attractive vehicle for cancer gene therapy due to their high efficiency of gene delivery. Many viruses can mediate long term gene expression, while some are also capable of infecting both dividing and non-dividing cells. Given the broadly differing capabilities of various viral vectors, it is imperative that the functionality of the virus meets the requirements of the specific treatment. A number of immunogene therapy strategies have been undertaken, utilising a range of viral vectors, and studies carried out in animal models and patients have demonstrated the therapeutic potential of viral vectors to carry genes to cancer cells and induce anti-tumour immune responses. This review critically discusses the advances in the viral vector mediated delivery of immunostimulatory molecules directly to tumour cells, the use of viral vectors to modify tumour cells, the creation of whole cell vaccines and the direct delivery of tumour antigens in animal models and clinical trials, specifically in the context of the suitability of vector types for specific strategies.
en
viral vectors
cancer immunotherapy
Viral vectors in cancer immunotherapy: which vector for which strategy?
Article
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oai:uobrep.openrepository.com:10547/2245802020-04-23T07:35:00Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Smits, Evelien L.J.
author
Lee, Cindy
author
Hardwick, Nicola R.
author
Brooks, Suzanne E.
author
Van Tendeloo, Viggo F.I.
author
Orchard, Kim H.
author
Guinn, Barbara-Ann
department
University of Antwerp
2012-05-18T10:44:52Z
2011-06
Smits, E.L.J., Lee, C., Hardwick, N., Brooks, S.E., Van Tendeloo, V.F.I., Orchard, K., Guinn, B.A. (2011) 'Clinical evaluation of cellular immunotherapy in acute myeloid leukaemia' Cancer immunology, immunotherapy, 60 (6):757-69
1432-0851
21519825
10.1007/s00262-011-1022-6
http://hdl.handle.net/10547/224580
Cancer immunology, immunotherapy : CII
Immunotherapy is currently under active investigation as an adjuvant therapy to improve the overall survival of patients with acute myeloid leukaemia (AML) by eliminating residual leukaemic cells following standard therapy. The graft-versus-leukaemia effect observed following allogeneic haematopoietic stem cell transplantation has already demonstrated the significant role of immune cells in controlling AML, paving the way to further exploitation of this effect in optimized immunotherapy protocols. In this review, we discuss the current state of cellular immunotherapy as adjuvant therapy for AML, with a particular focus on new strategies and recently published results of preclinical and clinical studies. Therapeutic vaccines that are being tested in AML include whole tumour cells as an autologous source of multiple leukaemia-associated antigens (LAA) and autologous dendritic cells loaded with LAA as effective antigen-presenting cells. Furthermore, adoptive transfer of cytotoxic T cells or natural killer cells is under active investigation. Results from phase I and II trials are promising and support further investigation into the potential of cellular immunotherapeutic strategies to prevent or fight relapse in AML patients.
en
acute myeloid leukaemia
clinical immunotherapy
clinical trials
Clinical evaluation of cellular immunotherapy in acute myeloid leukaemia.
Article
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oai:uobrep.openrepository.com:10547/2245552019-01-25T11:15:53Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
author
Greiner, Jochen
author
Schmitt, Michael
author
Mills, Ken I.
2012-05-18T10:41:42Z
2009-01-29
Guinn, B.A., Greiner, J., Schmitt, M., Mills, K.I. (2009) 'Elevated expression of the leukemia-associated antigen SSX2IP predicts survival in acute myeloid leukemia patients who lack detectable cytogenetic rearrangements' Blood 113 (5):1203-4
1528-0020
19179477
10.1182/blood-2008-09-178848
http://hdl.handle.net/10547/224555
Blood
en
SSX2IP
acute myeloid leukaemia
survival
tumour antigen expression
Elevated expression of the leukemia-associated antigen SSX2IP predicts survival in acute myeloid leukemia patients who lack detectable cytogenetic rearrangements.
Article
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
oai:uobrep.openrepository.com:10547/2245432018-05-14T09:31:02Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Mohamedali, Azim
author
Guinn, Barbara-Ann
author
Sahu, Satyajit
author
Thomas, N.S.
author
Mufti, Ghulam J.
2012-05-18T08:49:24Z
2009-01
Mohamedali, A. et al (2009) 'Serum profiling reveals distinctive proteomic markers in chronic myeloid leukaemia patients' Br. J. Haematol. 144 (2):263-5
1365-2141
19016716
10.1111/j.1365-2141.2008.07434.x
http://hdl.handle.net/10547/224543
British journal of haematology
en
serum profiling
chronic myeloid leukaemia
proteomic profiling
Serum profiling reveals distinctive proteomic markers in chronic myeloid leukaemia patients
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oai:uobrep.openrepository.com:10547/2245782020-04-23T07:35:03Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Greiner, Jochen
author
Bullinger, Lars
author
Guinn, Barbara-Ann
author
Döhner, Hartmut
author
Schmitt, Michael
department
University of Ulm
2012-05-18T10:39:02Z
2008-11-15
Greiner, J., Bullinger, L., Guinn, B.A., Döhner, H., Schmitt, M. (2008) 'Leukemia-associated antigens are critical for the proliferation of acute myeloid leukemia cells' Clinical cancer research 14 (22):7161-6
1078-0432
19010831
10.1158/1078-0432.CCR-08-1102
http://hdl.handle.net/10547/224578
Clinical cancer research : an official journal of the American Association for Cancer Research
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. With intensive induction therapy, most patients younger than 60 years achieve complete remission. However, even if these younger patients were treated intensively, more than 50% will relapse. Clinical results of patients older than 60 years are more unfavorable. Therefore, in all patients with AML, the overall survival is still low. In the past decade, several leukemia-associated antigens (LAA) have been identified in patients with acute myeloid leukemia. BAGE, BCL-2, OFA-iLRP, FLT3-ITD, G250, hTERT, PRAME, proteinase 3, RHAMM, survivin, and WT-1 are all LAAs that have been shown to induce CD8+ T-cell recognition and for some antigens also humoral immune responses. Interestingly, most of these LAAs are linked to cell cycle or proliferation. This article discusses the balance between LAA-driven leukemia cell expansion and the elimination of these cells through attacks on LAAs by the immune system. Current knowledge of the function and CD8+ T-cell recognition of LAAs is reviewed and an outlook is given on how to improve T-cell responses to LAAs in acute myeloid leukemia cells.
en
acute myeloid leukaemia
leukaemia associated antigens
cell proliferation
Leukemia-associated antigens are critical for the proliferation of acute myeloid leukemia cells.
Article
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oai:uobrep.openrepository.com:10547/2245772020-04-23T07:35:08Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
author
Casey, Garrett
author
Collins, Sara A.
author
O'Brien, Tim
author
Alexander, M. Yvonne
author
Tangney, Mark
department
King's College London
2012-05-18T10:34:34Z
2008-10
Guinn, B.A., Casey, G., Collins, S.A., O'Brien, T., Alexander, M.Y., Tangney, M. (2008) 'Tripartite meeting in gene and cell therapy, : Irish Society for Gene and Cell Therapy, British Society for Gene Therapy, and International Society for Cell and Gene Therapy of Cancer' Human gene therapy 19 (10):967-78
1557-7422
18652546
10.1089/hum.2008.085
http://hdl.handle.net/10547/224577
Human gene therapy
The second annual meeting of the Irish Society for Gene and Cell Therapy was held in Cork, Ireland on May 15 and 16, 2008 (http://crr.ucc.ie/isgct/). The meeting was jointly organized with the British Society for Gene Therapy and the International Society for Cell and Gene Therapy of Cancer. Because of the location of the conference and the co-organization of this meeting with the British and International Gene Therapy societies, the meeting enjoyed a range of talks from some of the major leaders in the field. Particularly notable were the talented molecular and cell biologists from Ireland who have contributed cutting edge science to the field of gene therapy. Topics including cardiovascular disease, repair of single-gene disorders, and cancer gene therapy were discussed with presentations ranging from basic research to translation into the clinic. Here we describe some of the most exciting presentations and their potential impact on imminent clinical gene therapy trials.
en
meeting report
gene and cell therapy
cancer gene therapy
Tripartite meeting in gene and cell therapy, 2008: Irish Society for Gene and Cell Therapy, British Society for Gene Therapy, and International Society for Cell and Gene Therapy of Cancer.
Article
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oai:uobrep.openrepository.com:10547/2245422019-01-25T11:16:12Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
author
Bullinger, Lars
author
Thomas, N. Shaun B.
author
Mills, Ken I.
author
Greiner, Jochen
2012-05-18T08:41:43Z
2008-01
Guinn, B-A. et al (2008) 'SSX2IP expression in acute myeloid leukaemia: an association with mitotic spindle failure in t(8;21), and cell cycle in t(15;17) patients' British Journal of Haematology 140 (2):250-1
1365-2141
18028484
10.1111/j.1365-2141.2007.06892.x
http://hdl.handle.net/10547/224542
British journal of haematology
en
SSX2IP
acute myeloid leukaemia
cytogenetic abnormalities
t(15;17)
t(8;21)
mitotic spindle failure
SSX2IP expression in acute myeloid leukaemia: an association with mitotic spindle failure in t(8;21), and cell cycle in t(15;17) patients
Article
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oai:uobrep.openrepository.com:10547/2245732020-04-23T07:35:27Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Cheuk, Adam T.C.
author
Guinn, Barbara-Ann
department
King's College London School of Medicine
2012-05-18T10:13:11Z
2008
Cheuk, A. & Guinn, B. (2008) 'Immunotherapy of acute myeloid leukaemia: development of a whole cell vaccine', Frontiers in Bioscience: a journal and virtual library, 13, pp.2022-2029.
1093-4715
17981688
http://hdl.handle.net/10547/224573
Frontiers in Bioscience : a journal and virtual library
Acute myeloid leukaemia (AML) is a difficult to treat disease and strategies, such as immunotherapy, which have the potential to eliminate residual tumour cells at first remission are required to reduce the incidence of relapse with its high associated mortality rates. T cells play an important role in tumor immunity and two signals are traditionally thought to be required to activate naive T cells; signal one through the major histocompatibility:antigen:T-cell receptor complex and signal two through costimulation. Many tumor associated antigens have been identified in AML suggesting it may be possible to target the immune system of AML patients; however AML develops due to tumour and immune editing, two systems by which AML cells can escape immune surveillance. By genetically modifying AML cells to express costimulatory molecules and/or cytokines, it has been possible to transform AML cells into antigen presenting cells and this has the potential to re-activate the immune system in patients. Here we summarize the rationale for using a whole cell vaccine approach to treat AML, and discuss current progress in the field of whole cell vaccine development against AML.
en
immunotherapy
acute myeloid leukaemia
whole cell vaccine
Immunotherapy of acute myeloid leukaemia: development of a whole cell vaccine.
Article
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oai:uobrep.openrepository.com:10547/2283172018-05-14T09:28:21Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Umansky, Viktor
author
Guinn, Barbara-Ann
2012-06-11T10:26:38Z
2010
ESCII–PIVAC meeting “Recent advances in cancer immunotherapy with an emphasis on cancer vaccines” held in Athens, 9–11 October 2008, 2010, 59 (4):635-640 Cancer Immunology, Immunotherapy
0340-7004
10.1007/s00262-009-0664-0
http://hdl.handle.net/10547/228317
Cancer Immunology, Immunotherapy
en
ESCII–PIVAC meeting “Recent advances in cancer immunotherapy with an emphasis on cancer vaccines” held in Athens, 9–11 October 2008
Article
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oai:uobrep.openrepository.com:10547/2287372018-06-25T13:16:40Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Favé, Gaëlle
author
Zhou, S.
author
Beckmann, M.E.
author
Harold, Graham
author
Lin, Wanchang
author
Tailliart, K.N.
author
Draper, J.H.
author
Mathers, John C.
department
Newcastle University
department
Aberystwyth University
2012-06-13T11:12:57Z
2010
Favé, G., Zhou, S., Beckmann, M.E., Harold, G., Lin, W., Tailliart, K.N., Draper, J.H., Mathers, J.C. (2010) 'The MEtabolomics to characterise Dietary Exposure (MEDE) Study: kinetics of metabolite responses to a test breakfast', Proceedings of the Nutrition Society 69 (OCE1)
0029-6651
10.1017/S0029665109992758
http://hdl.handle.net/10547/228737
Proceedings of the Nutrition Society
en
Measurement of dietary exposure
metabolomics
The MEtabolomics to characterise Dietary Exposure (MEDE) Study: kinetics of metabolite responses to a test breakfast
Article
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oai:uobrep.openrepository.com:10547/5787432020-04-23T07:34:55Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Khan, Ghazala
author
Brooks, Suzanne E.
author
Mills, Ken I.
author
Guinn, Barbara-Ann
department
University of Bedfordshire
department
Southampton General Hospital
department
Queen’s University Belfast
2015-09-25T10:03:20Z
2015-08
Khan, G., Brooks, S.E., Mills, K.I. & Guinn, B.A. (2015) 'Infrequent expression of the cancer-testis antigen, PASD1, in ovarian cancer' Biomarkers in Cancer, Vol 7, pp.31-38.
1179-299X
10.4137/BIC.S28378
http://hdl.handle.net/10547/578743
Biomarkers in Cancer
PMC4539101
Ovarian cancer is very treatable in the early stages of disease; however, it is usually detected in the later stages, at which time, treatment is no longer as effective. If discovered early (Stage I), there is a 90% chance of five-year survival. Therefore, it is imperative that early-stage biomarkers are identified to enhance the early detection of ovarian cancer. Cancer-testis antigens (CTAs), such as Per ARNT SIM (PAS) domain containing 1 (PASD1), are unique in that their expression is restricted to immunologically restricted sites, such as the testis and placenta, which do not express MHC class I, and cancer, making them ideally positioned to act as targets for immunotherapy as well as potential biomarkers for cancer detection where expressed. We examined the expression of PASD1a and b in a number of cell lines, as well as eight healthy ovary samples, eight normal adjacent ovarian tissues, and 191 ovarian cancer tissues, which were predominantly stage I (n = 164) and stage II (n = 14) disease. We found that despite the positive staining of skin cancer, only one stage Ic ovarian cancer patient tissue expressed PASD1a and b at detectable levels. This may reflect the predominantly stage I ovarian cancer samples examined. To examine the restriction of PASD1 expression, we examined endometrial tissue arrays and found no expression in 30 malignant tumor tissues, 23 cases of hyperplasia, or 16 normal endometrial tissues. Our study suggests that the search for a single cancer-testes antigen/biomarker that can detect early ovarian cancer must continue.
en
biomarker
ovarian cancer
PASD1
human
cancer-testis antigen
cancer
Infrequent expression of the cancer-testis antigen, PASD1, in ovarian cancer
Article
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URL
https://uobrep.openrepository.com/bitstream/10547/578743/1/Infrequent%20expression%20of%20the%20cancer-testis%20antigen%2c%20PASD1%2c%20in%20ovarian%20cancer.pdf
File
MD5
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4142306
application/pdf
Infrequent expression of the cancer-testis antigen, PASD1, in ovarian cancer.pdf
URL
https://uobrep.openrepository.com/bitstream/10547/578743/5/Infrequent%20expression%20of%20the%20cancer-testis%20antigen%2c%20PASD1%2c%20in%20ovarian%20cancer.pdf.txt
File
MD5
83b5fe1884b7eb1687935500c3573eea
36993
text/plain
Infrequent expression of the cancer-testis antigen, PASD1, in ovarian cancer.pdf.txt
oai:uobrep.openrepository.com:10547/5787552020-04-23T07:34:54Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Collin, Joseph F.
author
Wells, James W.
author
Czepulkowski, Barbara
author
Lyne, Linden
author
Duriez, Patrick J.
author
Banham, Alison H.
author
Mufti, Ghulam J.
author
Guinn, Barbara-Ann
department
King's College London
department
University of Oxford
department
Southampton University Hospitals Trust
department
University of Bedfordshire
2015-09-25T09:49:03Z
2015-05
Collin, J.F., Wells, J., Czepulkowski, B., Lyne, L., Duriez, P., Banham, A.H., Mufti, G.J. & Guinn, B.A. (2015) 'A novel zinc finger gene, ZNF465, is inappropriately expressed in presentation acute myeloid leukaemia cells.' Genes, Chromosomes & Cancer, Vol. 54, pp. 288-302.
1098-2264
25706801
10.1002/gcc.22242
http://hdl.handle.net/10547/578755
Genes, Chromosomes & Cancer
To increase our knowledge of leukaemia-associated antigens, especially in acute myeloid leukaemia (AML) M4, we prepared a phage display cDNA library using mRNA from the bone marrow cells of a patient with AML M4 at diagnosis. We immunoscreened 10(6) pfu with autologous sera and identified an antigen which we named GKT-AML8. The cDNA showed more than 99% similarity to a sequence on 2q21.2 and 95% sequence similarity to a sequence on 19q13.3. These genes were named ZNF465 and ZNF466, respectively, following HUGO Gene Nomenclature Committee (HGNC) guidelines. Expressed sequence tag data suggests that both genes are transcriptionally active. ZNF465 and ZNF466 encode a 5' krüppel associated box domain typical of negative regulators of gene transcription. We have confirmed the translational start site in the +1 frame in a near-Kozak sequence that produces a 102 amino acid polypeptide from ZNF465. The high level of sequence similarity between ZNF465 and ZNF466 makes their transcripts almost indistinguishable by real-time polymerase chain reaction (RT-PCR). However, GKT-AML8 showed most sequence similarity to ZNF465 and no transcript matching the 3' ZNF466 sequence could be detected in patient samples or healthy volunteers. ZNF465/466 expression was detectable in 12/13 AML and 10/14 chronic myeloid leukaemia patients' samples but not in normal donor peripheral blood (0/8) or 0/3 bone marrow samples which had been separated into CD34(+) and CD34(-) samples. The altered expression of ZNF465/466 in patients' samples and its absence in healthy donor haematopoietic samples indicate that ZNF465 is overexpressed in early myeloid disease and as such may represent a promising target for immunotherapy.
en
leukaemia
acute myeloid leukaemia
ZNF465
A novel zinc finger gene, ZNF465, is inappropriately expressed in presentation acute myeloid leukaemia cells
Article
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oai:uobrep.openrepository.com:10547/5787422020-04-23T07:38:22Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Whelan, Maria C.
author
Casey, Garrett
author
Larkin, John O.
author
Guinn, Barbara-Ann
author
O'Sullivan, Gerald C.
author
Tangney, Mark
department
University College Cork
department
University of Bedfordshire
2015-09-25T09:30:54Z
2014-05-15
Whelan, M.C., Casey, G., O. Larkin, J., Guinn, B.A., O’Sullivan, G.C., & Tangney, M. (2014) 'Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.' PLoS ONE 9(5): e97602
1932-6203
24832130
10.1371/journal.pone.0097602
http://hdl.handle.net/10547/578742
PLoS ONE
PMC4022586
Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut.
en
cancer
tumours
T-cell
oral tolerance
regulatory T-cells
Oral tolerance to cancer can be abrogated by T regulatory cell inhibition
Article
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URL
https://uobrep.openrepository.com/bitstream/10547/578742/1/Oral%20tolerance%20to%20cancer%20can%20be%20abrogated%20by%20T%20regulatory%20cell%20inhibition.pdf
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1394574
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Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.pdf
URL
https://uobrep.openrepository.com/bitstream/10547/578742/8/Oral%20tolerance%20to%20cancer%20can%20be%20abrogated%20by%20T%20regulatory%20cell%20inhibition.pdf.txt
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MD5
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text/plain
Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.pdf.txt
oai:uobrep.openrepository.com:10547/5788062020-04-23T07:34:55Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Khan, Ghazala
author
Denniss, Frances
author
Mills, Ken I.
author
Pulford, Karen
author
Guinn, Barbara-Ann
department
University of Bedfordshire
2015-09-28T09:08:23Z
2013-10
Khan, G., Denniss, F., Mills, K.I., Pulford, K. & Guinn, B.A. (2013) 'PASD1: a promising target for the immunotherapy of haematological malignancies'. Journal of Genetic Syndromes & Gene Therapy, 4:186.
2157-7412
10.4172/2157-7412.1000186
http://hdl.handle.net/10547/578806
Journal of Genetic Syndromes & Gene Therapy
In general, there is a lack of good immunotherapy targets within the spectrum of haematological malignancies. However haematopoietic stem cell transplants and continuing antigen discovery have allowed further insight into how further improvements in outcomes for patients might be achieved. Most patients with haematological malignancies can be treated with conventional therapies such as radio- and chemotherapy and will attain first remission. However the removal of residual diseased cells is essential to prevent relapse and its associated high mortality. PASD1 is one of the most tissue restricted cancer-testis (CT) antigens with expression limited to primary spermatagonia in healthy tissue. However, characterisation of PASD1 expression in cancers has been predominantly focussed on haematological malignancies where the inappropriate expression of PASD1 was first identified. PASD1 has one of the highest frequencies of expression of all CT antigens in acute myeloid leukaemia, with some suggestion of its role as a biomarker in diffuse large B-cell lymphoma. Here we describe the characterisation of the function and expression patterns of PASD1 in cell lines and primary tissues. Development of DNA vaccines targeting PASD1 epitopes demonstrate effective ex vivo T-cell responses in terms of IFNγ secretion and tumour cell killing. Of particular note these vaccines have led to the destruction of cells which process and present endogenous PASD1 indicating that effectively primed CTLs could kill PASD1-positive tumour cells.
en
PASD
immunotherapy
cancer
tumour antigen
cancer-testis antigen
C550 Immunology
PASD1: a promising target for the immunotherapy of haematological malignancies
Article
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URL
https://uobrep.openrepository.com/bitstream/10547/578806/1/pasd-a-promising-target-for-the-immunotherapy-of-haematological-malignancies-2157-7412.1000186.pdf
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pasd-a-promising-target-for-the-immunotherapy-of-haematological-malignancies-2157-7412.1000186.pdf
URL
https://uobrep.openrepository.com/bitstream/10547/578806/5/pasd-a-promising-target-for-the-immunotherapy-of-haematological-malignancies-2157-7412.1000186.pdf.txt
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pasd-a-promising-target-for-the-immunotherapy-of-haematological-malignancies-2157-7412.1000186.pdf.txt
oai:uobrep.openrepository.com:10547/5787442020-04-23T07:34:48Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
author
Braidwood, Lynne
author
Parker, Alan
author
Peng, Kah-Whye
author
Seymour, Leonard
2015-09-25T13:12:55Z
2014-12
Guinn, B.A., Braidwood, L., Parker, A., Peng, K.W., & Seymour, L. (2014) '8th international conference on oncolytic virus therapeutics'. Human Gene Therapy, vol 25 (12) pp.1062-84
1557-7422
25274574
10.1089/hum.2014.118
http://hdl.handle.net/10547/578744
Human gene therapy
The 8th International Conference on Oncolytic Virus Therapeutics meeting was held from April 10-13, 2014, in Oxford, United Kingdom. It brought together experts in the field of oncolytics from Europe, Asia, Australasia, and the Americas and provided a unique opportunity to hear the latest research findings in oncolytic virotherapy. Presentations of recent work were delivered in an informal and intimate setting afforded by a small group of attendees and an exquisitely focused conference topic. Here we describe the oral presentations and enable the reader to share in the benefits of bringing together experts to share their findings.
en
8th international conference on oncolytic virus therapeutics
Article
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oai:uobrep.openrepository.com:10547/5788042018-05-14T09:23:04Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Khan, Ghazala
author
Guinn, Barbara-Ann
2015-09-28T09:03:52Z
2013
Khan G, Guinn BA. (2013) PASD1 (PAS domain containing 1). Atlas of Genetics and Cytogenetics in Oncology and Haematology. 17 (9) :630-632.
10.4267/2042/51427
http://hdl.handle.net/10547/578804
en
genetics
C400 Genetics
PASD1 (PAS domain containing 1)
Article
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URL
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URL
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04-2013-PASD1ID44567chXq28.pdf.txt
oai:uobrep.openrepository.com:10547/5788012020-04-23T07:33:08Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Witzens-Harig, Mathias
author
Hose, Dirk
author
Junger, Simone
author
Pfirschke, Christina
author
Khandelwal, Nisit
author
Umansky, Ludmilla
author
Seckinger, Anja
author
Conrad, Heinke
author
Brackertz, Bettina
author
Reme, Thierry
author
Gueckel, Brigitte
author
Meissner, Tobias
author
Hundemer, Michael
author
Ho, Anthony D.
author
Rossi, Jean-Francois
author
Neben, Kai
author
Bernhard, Helga
author
Goldschmidt, Hartmut
author
Klein, Bernard
author
Beckhove, Philipp
department
University Hospital of Heidelberg
department
Nationales Centrum für Tumorerkrankungen
department
German Cancer Research Center
department
Technische Universität, München
department
Institut National de la Santé et de la Recherche Médicale
department
Institute of Research in Biotherapy
department
Unité de Formation et de Recherche Médecine
department
University Hospital of Tübingen
department
Klinikum Darmstadt Gesellschaft mit beschränkter Haftung
2015-09-28T08:53:01Z
2013-04-19
Witzens-Harig, M., Hose, D., Junger, S., Pfirschke, C., Khandelwal, N., Umansky, L., Seckinger, A., Conrad, H., Brackertz, B., Rème, T., Gueckel, B., Meißner, T., Hundemer, M., Ho, A.D., Rossi, J.-F., Neben, K., Bernhard, H., Goldschmidt, H., Klein, B., Beckhove, P. (2013) 'Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6'. Blood 121 (22):4493
0006-4971
10.1182/blood-2012-05-429415
http://hdl.handle.net/10547/578801
Blood
Although functionally competent cytotoxic, T cells are frequently observed in malignant diseases, they possess little ability to react against tumor cells. This phenomenon is particularly apparent in multiple myeloma. We here demonstrate that cytotoxic T cells reacted against myeloma antigens when presented by autologous dendritic cells, but not by myeloma cells. We further show by gene expression profiling and flow cytometry that, similar to many other malignant tumors, freshly isolated myeloma cells expressed several carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) at varying proportions. Binding and crosslinking of CEACAM-6 by cytotoxic T cells inhibited their activation and resulted in T-cell unresponsiveness. Blocking of CEACAM-6 on the surface of myeloma cells by specific monoclonal antibodies or CEACAM-6 gene knock down by short interfering RNA restored T-cell reactivity against malignant plasma cells. These findings suggest that CEACAM-6 plays an important role in the regulation of CD8+ T-cell responses against multiple myeloma; therefore, therapeutic targeting of CEACAM-6 may be a promising strategy to improve myeloma immunotherapy.
en
Archived with thanks to Blood
tumors
tumours
tumour cells
multiple myeloma
T-cell
immunotherapy
Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6
Article
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
oai:uobrep.openrepository.com:10547/5788592020-04-23T07:35:06Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Hardwick, Nicola R.
author
Buchan, Sarah
author
Ingram, Wendy
author
Khan, Ghazala
author
Vittes, Gisella
author
Rice, Jason
author
Pulford, Karen
author
Mufti, Ghulam J.
author
Stevenson, Freda
author
Guinn, Barbara-Ann
department
King’s College London
department
University of Southampton
department
University of Bedfordshire
department
University of Oxford
2015-09-29T08:51:09Z
2013
Hardwick, N.R., Buchan, S., Ingram, W., Khan, G., Vittes, G., Rice, J., Pulford, K., Mufti, G.J., Stevenson, F.K. & Guinn, B.A. (2013) 'An analogue peptide from the cancer testis antigen, PASD1, induces CD8+ T cell-responses against naturally processed peptide'. Cancer Immunity, 13, pp.16-26.
1424-9634
23882161
http://hdl.handle.net/10547/578859
PMC3718735
We have previously identified the novel Cancer/Testis antigen PASD1 by immunoscreening a testis library with pooled acute myeloid leukemia (AML) patient sera. To develop a cytotoxic T lymphocyte (CTL)-inducing vaccine, we have now investigated the carboxy-terminal region, known to contain serological determinants, for MHC class I (HLA-A⋆0201)-binding peptides. Algorithm-selected natural peptides failed to show detectable HLA-A⋆0201 binding in T2 assays. However, anchor-modified analogue peptides showed enhanced binding, with decreased off-rates. Analogue peptide-loaded antigen-presenting cells (APCs) induced IFN-γ production by T cells from normal donors and patients. In addition, peptide-specific T cells could be expanded from cancer patients by stimulation with the PASD1 analogue peptide Pa14. For clinical application, a DNA fusion gene vaccine encoding Pa14 was designed and tested in "humanized" mice. Splenocytes from vaccinated mice showed in vitro cytotoxicity against tumour cells, either exogenously loaded with the corresponding wild-type peptide (Pw8) or expressing endogenously processed PASD1 protein. We show for the first time that a DNA vaccine encoding an altered PASD1 epitope can induce CTLs to target the natural peptide expressed by human tumour cells.
en
DNA vaccine
PASD1
acute myeloid leukemia
analogue peptide
immunotherapy
An analogue peptide from the cancer testis antigen, PASD1, induces CD8+ T cell-responses against naturally processed peptide.
Article
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URL
https://uobrep.openrepository.com/bitstream/10547/578859/2/130316.pdf
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oai:uobrep.openrepository.com:10547/5788742020-04-23T07:34:52Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Stafford, Richard
author
Smith, V.Anne
author
Husmeier, Dirk
author
Grima, Thomas
author
Guinn, Barbara-Ann
department
Bournemouth University
department
University of St Andrews
department
University of Glasgow
department
University of Bedfordshire
2015-09-29T08:43:17Z
2013
Stafford, R., Smith, V.A., Husmeier, D., Grima, T. & Guinn, B.A. (2013) 'Predicting ecological regime shift under climate change: new modelling techniques and potential of molecular-based approaches'. Current Zoology (59) pp403-417.
1674-5507
http://hdl.handle.net/10547/578874
Ecological regime shift is the rapid transition from one stable community structure to another, often ecologically inferior, stable community. Such regime shifts are especially common in shallow marine communities, such as the transition of kelp forests to algal turfs that harbour far lower biodiversity. Stable regimes in communities are a result of balanced interactions between species, and predicting new regimes therefore requires an evaluation of new species interactions, as well as the resilience of the ‘stable’ position. While computational optimisation techniques can predict new potential regimes, predicting the most likely community state of the various options produced is currently educated guess work. In this study we integrate a stable regime optimisation approach with a Bayesian network used to infer prior knowledge of the likely stress of climate change (or, in practice, any other disturbance) on each component species of a representative rocky shore community model. Combining the results, by calculating the product of the match between resilient computational predictions and the posterior probabilities of the Bayesian network, gives a refined set of model predictors, and demonstrates the use of the process in determining community changes, as might occur through processes such as climate change. To inform Bayesian priors, we conduct a review of molecular approaches applied to the analysis of the transcriptome of rocky shore organisms, and show how such an approach could be linked to measureable stress variables in the field. Hence species-specific microarrays could be designed as biomarkers of in situ stress, and used to inform predictive modelling approaches such as those described here.
en
regime shift
phase shift
alternative stable state
intertidal
food web
resilience
Predicting ecological regime shift under climate change: new modelling techniques and potential of molecular-based approaches
Article
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oai:uobrep.openrepository.com:10547/5788532018-05-14T09:23:16Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Khan, Ghazala
author
Guinn, Barbara-Ann
department
University of Bedfordshire
2015-09-29T08:21:20Z
2012-03
Khan, G. & Guinn, B.A. (2012) 'SSX2IP Synovial Sarcoma, X breakpoint 2 interacting protein'. Atlas of Genetics and Cytogenetics in Oncology and Haematology, 16, 552-554.
10.4267/2042/47489
http://hdl.handle.net/10547/578853
en
genetics
cytogenetics
C400 Genetics
SSX2IP Synovial Sarcoma, X breakpoint 2 interacting protein
Article
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URL
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oai:uobrep.openrepository.com:10547/5788582019-01-25T11:15:28Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Liberante, Fabio G.
author
Pellagatti, Andrea
author
Boncheva, Viktoriya Bogdanova
author
Bowen, David T.
author
Mills, Ken I.
author
Boultwood, Jacqueline
author
Guinn, Barbara-Ann
institution
University of Bedfordshire
institution
Leeds Teaching Hospitals NHS Trust
institution
Queens University Belfast
institution
John Radcliffe Hospital
2015-09-29T08:37:32Z
2013-07
Liberante, F.G., Pellagatti, A., Boncheva, V., Bowen, D.T., Mills, K.I., Boultwood, J. & Guinn, B.A. (2013) 'High and low, but not intermediate, PRAME expression levels are poor prognostic markers in myelodysplastic syndrome at disease presentation' British Journal of Haematology. 162 (2) pp 282-284.
0007-1048
10.1111/bjh.12352
http://hdl.handle.net/10547/578858
British Journal of Haematology
en
myelodysplastic syndrome
tumour antigens
Preferentially expressed Antigen of the Melanoma Gene
leukaemia antigens
survival
High and low, but not intermediate, PRAME expression levels are poor prognostic markers in myelodysplastic syndrome at disease presentation
Article
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oai:uobrep.openrepository.com:10547/5788572020-04-23T07:34:48Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Boncheva, Viktoriya Bogdanova
author
Bonney, S.A.
author
Brooks, Suzanne E.
author
Tangney, Mark
author
O'Sullivan, Gerald C.
author
Mirnezami, A.
author
Guinn, Barbara-Ann
2015-09-29T08:33:58Z
2013-03-15
Boncheva, V., Bonney, S.A.., Brooks, S.E., Tangney, M., O'Sullivan, G.C., Mirnezami, A., Guinn, B.A. (2013) 'New targets for the immunotherapy of colon cancer—does reactive disease hold the answer?' Cancer Gene Therapy 20 (3):157
0929-1903
10.1038/cgt.2013.5
http://hdl.handle.net/10547/578857
Cancer Gene Therapy
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women, posing a serious demographic and economic burden worldwide. In the United Kingdom, CRC affects 1 in every 20 people and it is often detected once well established and after it has spread beyond the bowel (Stage IIA-C and Stage IIIA-C). A diagnosis at such advanced stages is associated with poor treatment response and survival. However, studies have identified two sub-groups of post-treatment CRC patients--those with good outcome (reactive disease) and those with poor outcome (non-reactive disease). We aim to review the state-of-the-art for CRC with respect to the expression of cancer-testis antigens (CTAs) and their identification, evaluation and correlation with disease progression, treatment response and survival. We will also discuss the relationship between CTA expression and regulatory T-cell (Treg) activity to tumorigenesis and tumor immune evasion in CRC and how this could account for the clinical presentation of CRC. Understanding the molecular basis of reactive CRC may help us identify more potent novel immunotherapeutic targets to aid the effective treatment of this disease. In this review, based on our presentation at the 2012 International Society for the Cell and Gene Therapy of Cancer annual meeting, we will summarize some of the most current advances in CTA and CRC research and their influence on the development of novel immunotherapeutic approaches for this common and at times difficult to treat disease.
en
cancer gene therapy
immunotherapy
colon cancer
reactive disease
New targets for the immunotherapy of colon cancer—does reactive disease hold the answer?
Article
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oai:uobrep.openrepository.com:10547/5788552020-04-23T07:34:49Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Lam, P.
author
Khan, Ghazala
author
Stripecke, R.
author
Hui, K.M.
author
Kasahara, N.
author
Peng, Kah-Whye
author
Guinn, Barbara-Ann
2015-09-29T08:09:02Z
2013-02-01
Lam, P., Khan, G., Stripecke, R., Hui, K.M., Kasahara, N., Peng, K.-W. & Guinn, B.A (2013) 'The innovative evolution of cancer gene and cellular therapies'. Cancer Gene Therapy, 20 (3) pp141-9
0929-1903
10.1038/cgt.2012.93
http://hdl.handle.net/10547/578855
Cancer Gene Therapy
We provide an overview of the latest developments in cancer gene therapy--from the bench to early-stage clinical trials. We describe the most recent work of worldwide teams including experienced scientists and clinicians, reflecting the recent emergence of gene therapy from the 'Valley of Death'. The treatment efficacy of clinical gene therapy has now been shown in a number of diseases including cancer and we are observing a renewed interest by big pharmaceutical and biotechnology companies most obviously demonstrated by Amgen's acquisition of Biovex for up to USD$1 billion. There is an opportunity to be cautiously hopeful regarding the future of gene therapy in the clinic and we review here some of the most recent progress in the field.
en
cancer gene therapy
cancer immunotherapy
cellular therapy
The innovative evolution of cancer gene and cellular therapies
Article
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oai:uobrep.openrepository.com:10547/5788562020-04-23T07:34:48Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Hofmann, Susanne
author
Khan, Ghazala
author
Boncheva, Viktoriya Bogdanova
author
Greiner, Jochen
author
Guinn, Barbara-Ann
2015-09-29T08:11:16Z
2014
Hofmann, S., Khan, G., Boncheva, V., Greiner, J. & Guinn, B.A. (2014) 'Vaccination against myeloid leukaemias using newly defined antigens'. In Rees, R (Ed) 'Cancer Immunology Immunotherapy'. Oxford University Press.
9780199676866
10.1093/med/9780199676866.001.0001
http://hdl.handle.net/10547/578856
First complete remission rates are high in patients with acute myeloid leukaemia (AML), with some variation depending on the presence of specific cytogenetic and molecular aberrations. However, the remission is often not long lasting and relapse occurs after standard chemotherapy within two years. Besides chemotherapy, non-specific immunotherapy in the form of allogeneic haematopoietic stem cell transplantation (HSCT) is an integral part of consolidation and salvage therapy in the treatment of AML. A large number of leukaemia-associated antigens (LAAs) that can act as potential targets for specific immunotherapy have been identified, and the number is still increasing. To date, several of these antigens are being utilized in clinical vaccination trials, either as active specific immunotherapy in form of peptide vaccination or as passive specific immunotherapy as adoptive cell therapies. This chapter reviews the role of newly defined LAAs as well as the results of already performed clinical vaccination trials with known LAAs.
en
myeloid leukaemia
vaccination
antigens
Vaccination against myeloid leukaemias using newly defined antigens
Book chapter
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oai:uobrep.openrepository.com:10547/5788512018-05-14T09:22:05Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Khan, Ghazala
author
Brooks, Suzanne E.
author
Denniss, Frances
author
Sigurdardottir, Dagmar
author
Guinn, Barbara-Ann
department
University of Bedfordshire
department
University of Southampton
department
King’s College London
department
University of Tübingen
2015-09-29T08:03:03Z
2013
Khan, G., Brooks, S.E., Denniss, F.K., Sigurdardottir, D. & Guinn, B.A. (2013) 'Identification and validation of targets for cancer immunotherapy: from the bench-to-bedside'. In Wei, M. & Good, D (Eds) 'Novel Gene Therapy Approaches' IntechOpen.
10.5772/54698
http://hdl.handle.net/10547/578851
en
gene and cell therapy
gene therapy
cancer gene therapy
cancer immunotherapy
C550 Immunology
Identification and validation of targets for cancer immunotherapy: from the bench-to-bedside
Book chapter
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oai:uobrep.openrepository.com:10547/5788502020-04-23T07:34:47Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
department
University of Bedfordshire
2015-09-29T07:46:14Z
2015-07
Guinn, B.A. (2015) 'Is there a need to identify novel tumour antigens as targets for immunotherapy clinical trials for the removal of minimal residual disease in haematological malignancies?' Invited submission. International Journal for Haematological Research, 1, pp24-26.
2409-3548
http://hdl.handle.net/10547/578850
International journal of hematology research
Despite the identification of many tumour antigens with the potential to act as targets for cancer vaccines and/or T-cell therapies very few have been used in clinical trials to date. This led to the timely development of a criteria which identified the ideal characteristics of tumour antigens which should be actively pursued for use in immunotherapy clinical trials. A list of 75 antigens were assessed against these criteria and although none harboured all of the characteristics identified as desirable, a number did show many of the characteristics identifying them as worthy of further pursuit to enable an organised development towards immunotherapy clinical trials. The study highlighted the benefit of focussing on a short list of antigens which would enable the rapid progress of a smaller number of antigens into clinical trials as targets for immunotherapy. However the antigens expressed by solid tumours often differ to those expressed by haematological malignancies, leading to this editorial which states the need for a similar study prioritising tumour antigens for use in clinical trials of haematological malignancies, independently of solid tumours. We also debate the importance of looking for new antigens in cancers in which few targets are known and discuss the importance of tumour antigens as biomarkers of disease diagnosis, stage and survival.
en
tumour antigens
immunotherapy
clinical trials
minimal residual disease
haematologocial malignancies
leukaemia
Is there a need to identify novel tumour antigens as targets for immunotherapy clinical trials for the removal of minimal residual disease in haematological malignancies?
Article
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oai:uobrep.openrepository.com:10547/5788542020-04-23T07:34:47Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Guinn, Barbara-Ann
department
University of Bedfordshire
2015-09-29T07:54:26Z
2014-12
Guinn, B.A. (2014) 'The future of publishing scientific data: is it time to accept the wider publication of null data?' EC Cancer 1, 1-2.
http://hdl.handle.net/10547/578854
EC Cancer
One of the most self-limiting dogmas’ which scientists submit themselves to is the avoidance of publishing negative data. This reflected the fact that authors generally do not write up and submit null data. The avoidance of publishing negative data (by authors and journals) ensures we only show experiments that worked and represent a clear story of success. Experiments which the research community remains ignorant of and which thus be repeated wasting the limited money currently available for research from the government and charities, and time which could be spent more productively, moving the field forward more rapidly. But how should the science community publish negative data? This Editorial discusses some of the concerns regarding publishing null data and ways we can move the bioscience forward through it's publication.
en
scientific data
data publishing
null data
scientific communication
science communication
The future of publishing scientific data: is it time to accept the wider publication of null data?
Article
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oai:uobrep.openrepository.com:10547/6008782020-04-23T07:35:05Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Brooks, Suzanne E.
author
Bonney, Stephanie A.
author
Lee, Cindy
author
Publicover, Amy
author
Khan, Ghazala
author
Smits, Evelien L.J.
author
Sigurdardottir, Dagmar
author
Arno, Matthew
author
Li, Demin
author
Mills, Ken I.
author
Pulford, Karen
author
Banham, Alison H.
author
van Tendeloo, Viggo
author
Mufti, Ghulam J.
author
Rammensee, Hans-Georg
author
Elliott, Tim J.
author
Orchard, Kim H.
author
Guinn, Barbara-Ann
2016-03-08T11:17:45Z
2015-10-22
Brooks SE, Bonney SA, Lee C, Publicover A, Khan G, Smits EL, et al. (2015) Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis 2015, 10 (10):e0140483 PLOS ONE
1932-6203
26492414
10.1371/journal.pone.0140483
http://hdl.handle.net/10547/600878
PLOS ONE
PMC4619595
Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.
en
Archived with thanks to PLOS ONE
C550 Immunology
immunotherapy
pMHC array
T-cell
T cell
leukaemia
leukaemia antigens
Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis
Article
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B Guinn Application of the pMHC array to characterise tumour antigen.PDF
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https://uobrep.openrepository.com/bitstream/10547/600878/6/B%20Guinn%20Application%20of%20the%20pMHC%20array%20to%20characterise%20tumour%20antigen.PDF.txt
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B Guinn Application of the pMHC array to characterise tumour antigen.PDF.txt
oai:uobrep.openrepository.com:10547/6011022020-04-23T07:34:43Zcom_10547_132178col_10547_132253
University of Bedfordshire Repository
author
Hofmann, Susanne
author
Mead, Andrew
author
Malinovskis, Aleksandrs
author
Hardwick, Nicola R.
author
Guinn, Barbara-Ann
department
University of Bedfordshire
2016-03-10T10:41:40Z
2015-10-05
Hofmann, S., Mead, A., Malinovskis, A., Hardwick, N.R., Guinn B. (2015) 'Analogue peptides for the immunotherapy of human acute myeloid leukemia'. Cancer Immunology, Immunotherapy 64 (11):1357-67
0340-7004
10.1007/s00262-015-1762-9
http://hdl.handle.net/10547/601102
Cancer Immunology, Immunotherapy
The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies.
en
Archived with thanks to Cancer Immunology, Immunotherapy
analogue peptides
adult acute myeloid leukemia
clinical trials
PASD1
heteroclitic peptides
NPM1
peptides
immunotherapy
C550 Immunology
Analogue peptides for the immunotherapy of human acute myeloid leukemia
Article
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URL
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2015 Hofmann et al peptide analogues review.pdf
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2015 Hofmann et al peptide analogues review.pdf.txt