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    Anti-tumor immunity in a model of acute myeloid leukemia

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    Authors
    Cheuk, Adam T.C.
    Wells, James W.
    Chan, Lucas
    Westwood, Nigel B.
    Berger, Stuart A.
    Yagita, Hideo
    Okumura, Ko
    Farzaneh, Farzin
    Mufti, Ghulam J.
    Guinn, Barbara-Ann
    Affiliation
    King's College London
    Issue Date
    2009-03
    Subjects
    whole cell vaccine
    acute myeloid leukaemia
    4-1BB ligand
    co-stimulatory molecules
    
    Metadata
    Show full item record
    Abstract
    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.
    Citation
    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.
    Publisher
    informa healthcare
    Journal
    Leukemia & lymphoma
    URI
    http://hdl.handle.net/10547/224557
    DOI
    10.1080/10428190802653776
    PubMed ID
    19197726
    19197726
    Additional Links
    http://www.tandfonline.com/doi/abs/10.1080/10428190802653776?journalCode=ilal20
    Type
    Article
    Language
    en
    ISSN
    1029-2403
    Sponsors
    Leukaemia and Lymphoma Research, Cancer Research U.K.
    ae974a485f413a2113503eed53cd6c53
    10.1080/10428190802653776
    Scopus Count
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    Biomedicine and Nutrition Research Group

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