Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer
Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer
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DOI：
10.1007/s00262-007-0355-7
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发表时间：
2008-02-01
影响因子：
5.8
通讯作者：
Peschel, Christian
中科院分区：
文献类型：
--
作者：
Bernhard, Helga;Neudorfer, Julia;Peschel, Christian
人表皮生长因子受体2 （HER2）已被基于HER2定向单克隆抗体和癌症疫苗的免疫治疗方法靶向为乳腺癌相关抗原。我们描述了自体her2特异性t淋巴细胞克隆对转移性her2过表达乳腺癌患者的过继转移。HLA/multi -based监测转移的T淋巴细胞显示T细胞迅速从外周血中消失。影像学研究显示，T细胞在骨髓（BM）中积聚并迁移到肝脏，但不能渗透到实体转移灶中。过继性t细胞治疗完成后，BM内弥散性肿瘤细胞消失。本研究提示了her2特异性T细胞在消除弥散性her2阳性肿瘤细胞方面的治疗潜力，并提出了基于T细胞的治疗与靶向肿瘤基质的策略相结合，以改善T细胞向实体瘤的浸润。
The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.