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Anti-tumor immunity in a model of acute myeloid leukemia

  • Adam T.C. Cheuk
    ,
  • James W. Wells
    ,
  • Lucas Chan
    ,
  • Nigel B. Westwood
    ,
  • Stuart A. Berger
    ,
  • Hideo Yagita
  • King's College London
    ,
  • University of Toronto
    ,
  • Juntendo University
Research Output: Contribution to journal Article Peer-review

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 447-454

Journal (Volume, Issue Number)

Leukemia and Lymphoma (Volume 50, Issue 3)

Publication milestones

  • Published - 01/03/2009

Publication status

Published - 01/03/2009

ISSN

1042-8194

External Publication IDs

  • handle.net: 10547/224557
  • Scopus: 67650873221

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