AuthorsCheuk, Adam T.C.
Wells, James W.
Westwood, Nigel B.
Berger, Stuart A.
Mufti, Ghulam J.
AffiliationKing's College London
MetadataShow full item record
AbstractWhole-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.
CitationCheuk, 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.
JournalLeukemia & lymphoma
SponsorsLeukaemia and Lymphoma Research, Cancer Research U.K.
- 4-1BBL cooperates with B7-1 and B7-2 in converting a B cell lymphoma cell line into a long-lasting antitumor vaccine.
- Authors: Guinn BA, DeBenedette MA, Watts TH, Berinstein NL
- Issue date: 1999 Apr 15
- Immunotherapy of acute myeloid leukaemia: development of a whole cell vaccine.
- Authors: Cheuk AT, Guinn BA
- Issue date: 2008 Jan 1
- Gene therapy with B7.1 and GM-CSF vaccines in a murine AML model.
- Authors: Dunussi-Joannopoulos K, Weinstein HJ, Arceci RJ, Croop JM
- Issue date: 1997 Nov-Dec
- Regulation of CD80/B7-1 and CD86/B7-2 molecule expression in human primary acute myeloid leukemia and their role in allogenic immune recognition.
- Authors: Costello RT, Mallet F, Sainty D, Maraninchi D, Gastaut JA, Olive D
- Issue date: 1998 Jan
- Development of a potent melanoma vaccine capable of stimulating CD8(+) T-cells independently of dendritic cells in a mouse model.
- Authors: Powell KL, Stephens AS, Ralph SJ
- Issue date: 2015 Jul