PHASE I STUDY OF ADOPTIVE IMMUNOTHERAPY AFTER STEM CELL TRANSPLANT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。同种异体造血细胞移植（HCT）后白血病的消除部分归因于一种被称为“移植物抗白血病”（GVL）效应的免疫反应，在这种效应中，残留的白血病细胞被供体T细胞与受体次要组织相容性(H)抗原反应破坏（1-7）。然而，在许多接受同种异体HCT的患者中，不足以根除潜在白血病的GVL效应未能形成，移植最终因恶性肿瘤复发而失败。通过过继转移来自供体的未选择的多克隆T淋巴细胞来增强GVL效果的尝试通常是不成功的，因为供体淋巴细胞输注（DLI）产生的持久的抗白血病反应很少，如果有的话，但由于移植物抗宿主病（GVHD）的发展导致了很多发病率和死亡率（8-11）。这项研究探讨了供体来源的CD8+细胞毒性T淋巴细胞（CTL）克隆的过继性转移是否可以作为一种毒性更小但更有效的治疗方法，治疗同种异体HCT后急性白血病复发的患者。CTL克隆特异于受体的次要组织相容性(H)抗原，这些抗原在造血细胞中表达，但在非造血细胞中表达有限。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The elimination of leukemia following allogeneic hematopoietic cell transplantation (HCT) is in part attributable to an immune response termed the "graft versus leukemia" (GVL) effect in which residual leukemia cells are thought to be destroyed by donor T cells reacting with recipient minor histocompatibility (H) antigens(1-7). In many patients who undergo allogeneic HCT, however, a GVL effect sufficient to eradicate the underlying leukemia fails to develop, and the transplant ultimately fails due to recurrence of the malignancy. Attempts to enhance the GVL effect through the adoptive transfer of unselected, polyclonal T lymphocytes from the donor have in general been unsuccessful because donor lymphocyte infusion (DLI) produces few, if any, durable antileukemic responses but causes much morbidity and mortality due to the development of graft-versus-host disease (GVHD)(8-11). This study addresses whether adoptive transfer of donor-derived CD8+ cytotoxic T lymphocyte (CTL) clones specific for minor histocompatibility (H) antigens of the recipient that are expressed in hematopoietic cells but have limited expression in non-hematopoietic cells can be a less toxic but more effective treatment for patients with recurrence of acute leukemia after allogeneic HCT.