Anti-tumor immunity in a model of acute myeloid leukemia.
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.
Cheuk
Adam T C
AT
Department of Haematological Medicine, Allergy & Respiratory Science, MRC/Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London School of Medicine, London, UK.
Wells
James W
JW
Chan
Lucas
L
Westwood
Nigel B
NB
Berger
Stuart A
SA
Yagita
Hideo
H
Okumura
Ko
K
Farzaneh
Farzin
F
Mufti
Ghulam J
GJ
Guinn
Barbara-Ann
BA
D053330:4-1BB Ligand / Q000276:immunology / Q000627:therapeutic use; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology / Q000627:therapeutic use; D051940:B7-2 Antigen / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D006801:Humans; D007109:Immunity; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice
D053330:4-1BB Ligand; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019496:Cancer Vaccines