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Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease

Nature Medicine volume 7, pages 789–794 (2001)Cite this article

Abstract

Adoptive transfer of T cells reactive to minor histocompatibility antigens has the unmatched ability to eradicate malignant hematopoietic cells. Unfortunately, its use is hampered by the associated graft-versus-host disease. The critical issue of a possible dissociation of the antileukemic effect and graft-versus-host disease by targeting specific minor histocompatibility antigens remains unresolved because of the unknown nature and number of minor histocompatibility antigens necessary or sufficient to elicit anti-leukemic activity and graft-versus-host disease. We found that injection of T lymphocytes primed against a single major histocompatibility complex class I-restricted immunodominant minor histocompatibility antigen (B6dom1) caused no graft-versus-host disease but produced a curative anti-leukemic response. Avoidance of graft-versus-host disease required that no other host-reactive T cells be co-injected with T cells primed with B6dom1. Here we show that effective and non-toxic immunotherapy of hematologic malignancies can be achieved by targeting a single immunodominant minor histocompatibility antigen.

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Figure 1: Survival of primed and unprimed mice following i.v. injection of 1× 105 EL4 cells
Figure 2: Assessment of B6dom1-specific CD8+ T cells by staining with B6dom1/Db tetramers.
Figure 3: B6dom1 is expressed on both hematopoietic and non-hematopoietic cells.
Figure 4: Adoptive transfer of B6dom1-primed T cells eradicates EL4 cells.

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Acknowledgements

We thank J.D. Altman for advice on the preparation of H2Db-peptide tetramers; C. Fortin for help with statistical analyses; P.M. Huet for advice on liver cell populations; P. Eden for thoughtful review of the manuscript; Compatigene Inc. for sharing their cell culture and HPLC facilities; the CANVAC Tetramer Core Facility for a gift of plasmid clones; and J.A. Kashul for editorial assistance. Grant 011189 from the National Cancer Institute of Canada supported this work.

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  1. Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada

    Pierre Fontaine, Guillaume Roy-Proulx, Laurent Knafo, Chantal Baron, Denis-Claude Roy & Claude Perreault

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  1. Pierre Fontaine
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Correspondence to Claude Perreault.

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Fontaine, P., Roy-Proulx, G., Knafo, L. et al. Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease. Nat Med 7, 789–794 (2001). https://doi.org/10.1038/89907

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