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.
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- Authors: Costello RT, Mallet F, Sainty D, Maraninchi D, Gastaut JA, Olive D
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