Dudley Mark E, Rosenberg Steven A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA.
Semin Oncol. 2007 Dec;34(6):524-31. doi: 10.1053/j.seminoncol.2007.09.002.
Adoptive cell transfer therapy has developed into a potent and effective treatment for patients with metastatic melanoma. Current application of this therapy relies on the ex vivo generation of highly active, highly avid tumor-reactive lymphocyte cultures from endogenous tumor infiltrating lymphocytes or on the genetic engineering of cells using antigen receptor genes to express de novo tumor antigen recognition. When autologous anti-tumor lymphocyte cultures are administered to patients with high-dose interleukin (IL)-2 following a lymphodepleting conditioning regimen, the cells can expand in vivo, traffic to tumor, and mediate tumor regression and durable objective clinical responses. Current investigation seeks to improve the methods for generating and administering the lymphocyte cultures, and future clinical trials aim to improve durable response rates and extend the patient populations that are candidates for treatment.
过继性细胞转移疗法已发展成为转移性黑色素瘤患者的一种有效治疗方法。目前该疗法的应用依赖于从内源性肿瘤浸润淋巴细胞中体外培养出高活性、高亲和力的肿瘤反应性淋巴细胞培养物,或利用抗原受体基因对细胞进行基因工程改造以表达全新的肿瘤抗原识别能力。当在淋巴细胞清除预处理方案后给患者注射高剂量白细胞介素(IL)-2的自体抗肿瘤淋巴细胞培养物时,这些细胞可在体内扩增,迁移至肿瘤部位,并介导肿瘤消退和持久的客观临床反应。当前的研究旨在改进淋巴细胞培养物的生成和给药方法,未来的临床试验旨在提高持久反应率并扩大适合治疗的患者群体。