title: Anti-tumor immunity in a model of acute myeloid leukemia.
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.
authors.affiliation: 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.
authors.forename: Adam T C
authors.initials: AT
authors.lastname: Cheuk
authors.forename: James W
authors.initials: JW
authors.lastname: Wells
authors.forename: Lucas
authors.initials: L
authors.lastname: Chan
authors.forename: Nigel B
authors.initials: NB
authors.lastname: Westwood
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Berger
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Barbara-Ann
authors.initials: BA
authors.lastname: Guinn
mesh_terms: 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
chemical_list: D053330:4-1BB Ligand; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019496:Cancer Vaccines