Cancer regression in patients after transfer of genetically engineered lymphocytes
Cancer regression in patients after transfer of genetically engineered lymphocytes
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DOI：
10.1126/science.1129003
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发表时间：
2006-10-06
期刊：
影响因子：
56.9
通讯作者：
Rosenberg, Steven A.
中科院分区：
文献类型：
--
作者：
Morgan, Richard A.;Dudley, Mark E.;Rosenberg, Steven A.
通过宿主免疫耗竭后淋巴细胞的过继转移，有可能介导转移性黑色素瘤患者的客观癌症消退。然而，在这种免疫治疗模式中肿瘤特异性T细胞的产生通常是有限的。在这里，我们报告的能力，具体赋予肿瘤识别自体外周血淋巴细胞通过使用逆转录病毒编码的T细胞受体。这些转导细胞在15例患者中的连续转移导致在输注后至少2个月内超过10%的外周血淋巴细胞水平的持久植入。我们观察到高持续水平的循环，工程细胞在输注后1年的两名患者谁都表现出客观的转移性黑色素瘤病变消退。这项研究表明，基因工程细胞的生物治疗癌症的治疗潜力。
Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.