Sussman J J, Shu S, Sondak V K, Chang A E
Division of Surgical Oncology, University of Michigan, Ann Arbor.
Ann Surg Oncol. 1994 Jul;1(4):296-306. doi: 10.1007/BF02303568.
Adoptive immunotherapy of malignancy involves the passive transfer of antitumor-reactive cells into a host in order to mediate tumor regression. Based on animal models, the transfer of immune lymphoid cells can eradicate widely disseminated tumors and establish long-term systemic immunity. Critical for successful adoptive immunotherapy is the ability to isolate large numbers of immune cells. For clinical therapy, it will require the development on in vitro methods to promote the sensitization and propagation of tumor-reactive cells. However, this is a formidable task since human cancers are postulated to be poorly immunogenic because of their spontaneous origins.
Human lymphoid cells for ex vivo activation and subsequent adoptive transfer have been derived from different sources, including peripheral blood, tumor, and lymph nodes. Peripheral blood lymphocytes can be incubated with interleukin 2 to generate lymphokine-activated killer (LAK) cells, which nonspecifically lyse autologous and allogeneic tumor cells in vitro. LAK cell therapy represented the earliest attempt to treat advanced human cancers, with encouraging results documented in patients with renal cell cancer and melanoma. From that experience, the use of more immunologically specific cellular agents with potentially greater therapeutic efficacy has been investigated. One approach uses tumor-infiltrating lymphocytes, which have been characterized experimentally to be more specific in tumor reactivity compared with LAK cells. Other techniques have involved the use of lymphoid cells derived from lymph nodes draining tumors or primed by tumor vaccines. In vitro activation of these cells with tumor antigen or anti-CD3 monoclonal antibody results in the generation of T cells that mediate the rejection of poorly immunogenic tumors in animal studies. These alternate methods are currently being evaluated in clinical studies.
Experimentally, cellular therapy is a potent method to eradicate progressive tumors. Initial clinical studies have demonstrated that this form of therapy is technically feasible and can result in meaningful antitumor responses. Advances in this area will require improved methods to sensitize, isolate, and expand tumor-reactive T cells for adoptive transfer.
恶性肿瘤的过继性免疫疗法涉及将抗肿瘤反应性细胞被动转移至宿主体内，以介导肿瘤消退。基于动物模型，免疫淋巴细胞的转移可根除广泛播散的肿瘤并建立长期的全身免疫。成功进行过继性免疫疗法的关键在于能够分离出大量免疫细胞。对于临床治疗而言，需要开发体外方法以促进肿瘤反应性细胞的致敏和增殖。然而，这是一项艰巨的任务，因为据推测人类癌症因其自发起源而免疫原性较差。
用于体外激活及随后过继性转移的人淋巴细胞来源于不同的来源，包括外周血、肿瘤和淋巴结。外周血淋巴细胞可与白细胞介素2一起孵育以产生淋巴因子激活的杀伤细胞（LAK细胞），其在体外可非特异性地裂解自体和同种异体肿瘤细胞。LAK细胞疗法是治疗晚期人类癌症的最早尝试，在肾细胞癌和黑色素瘤患者中取得了令人鼓舞的结果。基于该经验，人们对使用具有潜在更高治疗效果的免疫特异性更强的细胞制剂进行了研究。一种方法是使用肿瘤浸润淋巴细胞，经实验证明其与LAK细胞相比，对肿瘤的反应性更具特异性。其他技术涉及使用来自引流肿瘤的淋巴结或经肿瘤疫苗致敏的淋巴细胞。在动物研究中，用肿瘤抗原或抗CD3单克隆抗体在体外激活这些细胞会产生介导低免疫原性肿瘤排斥反应的T细胞。目前正在临床研究中评估这些替代方法。
在实验中，细胞疗法是根除进行性肿瘤的有效方法。初步临床研究表明，这种治疗形式在技术上是可行的，并且可产生有意义的抗肿瘤反应。该领域的进展将需要改进使肿瘤反应性T细胞致敏、分离和扩增以进行过继性转移的方法。
