用于B细胞恶性肿瘤过继性免疫治疗的CD19特异性T细胞的开发与应用

Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies.

作者信息

Cooper Laurence J N, Al-Kadhimi Zaid, DiGiusto David, Kalos Michael, Colcher David, Raubitschek Andrew, Forman Steve J, Jensen Michael C

机构信息

Division of Hematology and Hematopoietic Cell Transplantation Transplant, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA 91010-3000, USA.

出版信息

Blood Cells Mol Dis. 2004 Jul-Aug;33(1):83-9. doi: 10.1016/j.bcmd.2004.03.003.

DOI:10.1016/j.bcmd.2004.03.003

PMID:15223016

Abstract

The graft-versus-leukemia (GVL)-effect achieved by donor-derived T cells arising from transplanted allogeneic hematopoietic stem cells or given as donor-leukocyte infusions (DLI) after allogeneic transplant, demonstrates that donor-derived T cells can eradicate B-lineage malignancies. However, graft-versus-host-disease (GVHD) occurring after allogeneic hematopoietic stem-cell transplant (HSCT) or polyclonal DLI can limit the efficacy of these interventions. This toxicity can be avoided by using autologous T cells and/or tumor-specific cytotoxic T lymphocytes (CTLs). To generate antigen-specific T cells that can be derived from the allogeneic donor or the patient, we have genetically manipulated T cells to express a CD19-specific chimeric immunoreceptor. This renders T cells specific for CD19, a cell surface molecule found on B-lineage leukemia and lymphoma. This review will demonstrate the redirected specificity of CD19-specific T cells and implementation of clinical trials using these cellular agents.

摘要

移植的异基因造血干细胞产生的供体来源T细胞或异基因移植后作为供体白细胞输注（DLI）所实现的移植物抗白血病（GVL）效应，表明供体来源的T细胞可以根除B系恶性肿瘤。然而，异基因造血干细胞移植（HSCT）或多克隆DLI后发生的移植物抗宿主病（GVHD）会限制这些干预措施的疗效。通过使用自体T细胞和/或肿瘤特异性细胞毒性T淋巴细胞（CTL）可以避免这种毒性。为了产生可来源于异基因供体或患者的抗原特异性T细胞，我们对T细胞进行了基因改造，使其表达CD19特异性嵌合免疫受体。这使得T细胞对CD19具有特异性，CD19是一种在B系白血病和淋巴瘤中发现的细胞表面分子。本综述将展示CD19特异性T细胞的重定向特异性以及使用这些细胞制剂进行临床试验的实施情况。