Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens
Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens
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DOI：
10.1182/blood.v93.7.2336.407k26_2336_2341
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发表时间：
1999-04-01
期刊：
影响因子：
20.3
通讯作者：
Goulmy, E
中科院分区：
文献类型：
--
作者：
Mutis, T;Verdijk, R;Goulmy, E
同种异体骨髓移植（BMT）是一种常见的治疗血液系统恶性肿瘤。潜在恶性肿瘤的复发是治疗失败的主要原因。患者次要组织相容性抗原（mHags）特异性的供体源性细胞毒性T淋巴细胞（ctl）在移植物抗宿主病（GVHD）和移植物抗白血病（GVL）反应中发挥重要作用，mHags HA-1和HA-2在体内诱导HLA-A*0201限制性ctl，并且只在造血细胞上表达，包括白血病细胞和白血病前体，但不在成纤维细胞、角化细胞或肝细胞上表达。mHags HA-1和HA-2的化学性质是已知的。我们研究了从未引物的mHag HA-1和/或ha -2阴性的健康献血者体内产生mHag HA-1和HA-1特异性ctl的可行性。用HA-1和HA-2合成肽脉冲树突状细胞（dc）作为抗原呈递细胞（APC）刺激自体未引物CD8(+) T细胞。体外生成的HA-1和ha -2特异性ctl有效地溶解来自急性髓性白血病（AML）和急性淋巴性白血病（ALL）患者的白血病细胞。对非造血细胞未检测到溶解反应性。总之，我们提出了一种治疗BMT后复发性白血病且GVHD风险低的可行的新疗法。(C) 1999年由美国血液病学会出版。
Allogeneic bone marrow transplantation (BMT) is a common treatment of hematologic malignancies. Recurrence of the underlying malignancy is a major cause of treatment failure. Donor-derived cytotoxic T lymphocytes (CTLs) specific for patients' minor histocompatibility antigens (mHags) play an important role in both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) reactivities, mHags HA-1 and HA-2 induce HLA-A*0201-restricted CTLs in vivo and are exclusively expressed on hematopoietic cells, including leukemic cells and leukemic precursors, but not on fibroblasts, keratinocytes, or liver cells. The chemical nature of the mHags HA-1 and HA-2 is known. We investigated the feasibility of ex vivo generation of mHag HA-1- and HA-a-specific CTLs from unprimed mHag HA-1- and/or HA-2-negative healthy blood donors. HA-1 and HA-2 synthetic peptide-pulsed dendritic cells (DCs) were used as antigen-presenting cells (APC) to stimulate autologous unprimed CD8(+) T cells. The ex vivo-generated HA-1- and HA-2-specific CTLs efficiently lyse leukemic cells derived from acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) patients. No lytic reactivity was detected against nonhematopoietic cells. Sufficient numbers of the CTLs can be obtained for the adoptive immunotherapy purposes, In conclusion, we present a feasible, novel therapy for the treatment for relapsed leukemia after BMT with a low risk of GVHD. (C) 1999 by The American Society of Hematology.