Bear Adham S, Fraietta Joseph A, Narayan Vivek K, O'Hara Mark, Haas Naomi B
Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Am Soc Clin Oncol Educ Book. 2021 Mar;41:57-65. doi: 10.1200/EDBK_321115.
Cancer immunotherapy tools include antibodies, vaccines, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies. This review will focus on adoptive cellular therapy, which involves the isolation of a patient's own immune cells followed by their ex vivo expansion and reinfusion. The majority of adoptive cellular therapy strategies utilize T cells isolated from tumor or peripheral blood, but may utilize other immune cell subsets. T-cell therapies in the form of tumor-infiltrating lymphocytes, T-cell receptor T cells, and CAR T cells may act as "living drugs" as these infused cells expand, engraft, and persist in vivo, allowing adaptability over time and enabling durable remissions in subsets of patients. Adoptive cellular therapy has been less successful in the management of solid tumors because of poor homing, proliferation, and survival of transferred cells. Strategies are discussed, including expression of transgenes to address these hurdles. Additionally, advances in gene editing using CRISPR/Cas9 and similar technologies are described, which allow for clinically translatable gene-editing strategies to enhance the antitumor activity and to surmount the hostilities advanced by the host and the tumor. Finally, the common toxicities and approaches to mitigate these are reviewed.
癌症免疫治疗工具包括抗体、疫苗、细胞因子、溶瘤病毒、双特异性分子和细胞疗法。本综述将聚焦于过继性细胞疗法，该疗法涉及分离患者自身的免疫细胞，然后在体外进行扩增并重新注入体内。大多数过继性细胞疗法策略利用从肿瘤或外周血中分离出的T细胞，但也可能利用其他免疫细胞亚群。肿瘤浸润淋巴细胞、T细胞受体T细胞和嵌合抗原受体T细胞形式的T细胞疗法可作为“活药物”，因为这些注入的细胞在体内扩增、植入并持续存在，随着时间推移具有适应性，并能使部分患者实现持久缓解。由于转移细胞的归巢、增殖和存活不佳，过继性细胞疗法在实体瘤治疗中成效较差。文中讨论了相关策略，包括通过表达转基因来克服这些障碍。此外，还描述了使用CRISPR/Cas9及类似技术进行基因编辑的进展，这些进展使得临床上可转化的基因编辑策略得以增强抗肿瘤活性，并克服宿主和肿瘤带来的不利因素。最后，综述了常见毒性以及减轻这些毒性的方法。
