Visioni Anthony, Skitzki Joseph
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Cancers (Basel). 2016 Sep 20;8(9):86. doi: 10.3390/cancers8090086.
A significant function of the immune system is the surveillance and elimination of aberrant cells that give rise to cancer. Even when tumors are well established and metastatic, immune-mediated spontaneous regressions have been documented. While there are have been various forms of immunotherapy, one of the most widely studied for almost 40 years is adoptive cellular immunotherapy, but its success has yet to be fully realized. Adoptive cell transfer (ACT) is a therapeutic modality that has intrigued physicians and researchers for its many theoretical benefits. Preclinical investigations and human trials have utilized natural killer (NK) cells, dendritic cells (DC), macrophages, T-cells or B-cells for ACT with the most intense research focused on T-cell ACT. T-cells are exquisitely specific to the target of its T-cell receptor (TCR), thus potentially reducing the amount of collateral damage and off-target effects from treatment. T-cells also possess a memory subset that may reduce the risk of recurrence of a cancer after the successful treatment of the primary disease. There are several options for the source of T-cells used in the generation of cells for ACT. Perhaps the most widely known source is T-cells generated from tumor-infiltrating lymphocytes (TILs). However, studies have also employed peripheral blood mononuclear cells (PBMCs), lymph nodes, and even induced pluripotent stem cells (IPSCs) as a source of T-cells. Several important technical considerations exist regarding benefits and limitations of each source of T-cells. Unique aspects of T-cells factor into their ability to be efficacious in ACT including the total number of cells available for ACT, the anti-tumor efficacy on a per cell basis, the repertoire of TCRs specific to tumor cells, and their ability to traffic to various organs that harbor tumor. Current research is attempting to unlock the full potential of these cells to effectively and safely treat cancer.
免疫系统的一项重要功能是监测和清除会引发癌症的异常细胞。即便肿瘤已经形成并发生转移，免疫介导的自发消退也有记录。虽然存在多种形式的免疫疗法，但近40年来研究最为广泛的一种是过继性细胞免疫疗法，不过其成效尚未完全显现。过继性细胞移植（ACT）是一种治疗方式，因其诸多理论优势而引起了医生和研究人员的兴趣。临床前研究和人体试验已将自然杀伤（NK）细胞、树突状细胞（DC）、巨噬细胞、T细胞或B细胞用于ACT，其中对T细胞ACT的研究最为深入。T细胞对其T细胞受体（TCR）的靶标具有高度特异性，因此有可能减少治疗带来的附带损害和脱靶效应。T细胞还拥有一个记忆亚群，这可能会降低原发性疾病成功治疗后癌症复发的风险。用于生成ACT细胞的T细胞来源有几种选择。或许最广为人知的来源是肿瘤浸润淋巴细胞（TIL）产生的T细胞。然而，研究也采用外周血单个核细胞（PBMC）、淋巴结，甚至诱导多能干细胞（iPSC）作为T细胞来源。关于每种T细胞来源的益处和局限性，存在几个重要的技术考量因素。T细胞的独特特性涉及其在ACT中发挥功效的能力，包括可用于ACT的细胞总数、单个细胞的抗肿瘤功效、肿瘤细胞特异性TCR的库以及它们迁移到含有肿瘤的各个器官的能力。当前的研究正试图释放这些细胞的全部潜能，以有效且安全地治疗癌症。
