Anti-tumour immunity in a model of acute myeloid leukaemia

Cheuk, Adam T.C., Wells, James W., Chan, Lucas, Westwood, Nigel B., Berger, Stuart A., Yagita, Hideo, Okumura, Ko, Farzin, Farzin, Mufti, Ghulam J. and Guinn, Barbara-Anne (2009) Anti-tumour immunity in a model of acute myeloid leukaemia. Leukemia and Lymphoma, 50 (3), 447-454. (doi:10.1080/10428190802653776).

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 ostimulatory molecules

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