Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease.
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.
Fontaine
P
P
Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada.
Roy-Proulx
G
G
Knafo
L
L
Baron
C
C
Roy
D C
DC
Perreault
C
C
D019264:Adoptive Transfer; D000818:Animals; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D007167:Immunotherapy; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015778:Minor Histocompatibility Antigens