Fontaine P, Roy-Proulx G, Knafo L, Baron C, Roy D C, Perreault C
Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada.
Nat Med. 2001 Jul;7(7):789-94. doi: 10.1038/89907.
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.
过继转输对次要组织相容性抗原具有反应性的T细胞，在根除恶性造血细胞方面有着无与伦比的能力。不幸的是，移植物抗宿主病限制了其应用。由于引发抗白血病活性和移植物抗宿主病所需或足以引发这些反应的次要组织相容性抗原的性质和数量未知，通过靶向特定次要组织相容性抗原实现抗白血病效应与移植物抗宿主病可能解离这一关键问题仍未得到解决。我们发现，注射针对单一主要组织相容性复合体I类限制性免疫显性次要组织相容性抗原（B6dom1）致敏的T淋巴细胞不会引发移植物抗宿主病，但会产生治愈性的抗白血病反应。避免移植物抗宿主病要求不能将其他对宿主有反应性的T细胞与用B6dom1致敏的T细胞共同注射。在此我们表明，通过靶向单一免疫显性次要组织相容性抗原可实现对血液系统恶性肿瘤的有效且无毒的免疫治疗。
