Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease
| Autor: | Denis-Claude Roy, Pierre Fontaine, Claude Perreault, Laurent Knafo, Chantal Baron, Guillaume Roy-Proulx |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adoptive cell transfer
Leukemia Experimental biology T-Lymphocytes medicine.medical_treatment Antigen presentation Graft vs Host Disease General Medicine Immunotherapy Flow Cytometry Major histocompatibility complex medicine.disease Adoptive Transfer General Biochemistry Genetics and Molecular Biology Minor Histocompatibility Antigens Mice Graft-versus-host disease Antigen Immunology medicine biology.protein Minor histocompatibility antigen Animals Antigen-presenting cell |
| Zdroj: | Nature Medicine. 7:789-794 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/89907 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|