Department of Pathology, The Ohio State University, Columbus, OH, United States.
The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, United States.
Front Immunol. 2021 Jun 1;12:690499. doi: 10.3389/fimmu.2021.690499. eCollection 2021.
The rationale behind cancer immunotherapy is based on the unequivocal demonstration that the immune system plays an important role in limiting cancer initiation and progression. Adoptive cell therapy (ACT) is a form of cancer immunotherapy that utilizes a patient's own immune cells to find and eliminate tumor cells, however, donor immune cells can also be employed in some cases. Here, we focus on T lymphocyte (T cell)-based cancer immunotherapies that have gained significant attention after initial discoveries that graft-versus-tumor responses were mediated by T cells. Accumulating knowledge of T cell development and function coupled with advancements in genetics and data science has enabled the use of a patient's own (autologous) T cells for ACT (TIL ACTs). In TIL ACT, tumor-infiltrating lymphocytes (TILs) are collected from resected tumor material, enhanced and expanded , and delivered back to the patient as therapeutic agents. ACT with TILs has been shown to cause objective tumor regression in several types of cancers including melanoma, cervical squamous cell carcinoma, and cholangiocarcinoma. In this review, we provide a brief history of TIL ACT and discuss the current state of TIL ACT clinical development in solid tumors. We also discuss the niche of TIL ACT in the current cancer therapy landscape and potential strategies for patient selection.
癌症免疫疗法的基本原理基于一个明确的证据,即免疫系统在限制癌症的发生和进展方面起着重要作用。过继细胞疗法(ACT)是一种癌症免疫疗法,利用患者自身的免疫细胞来寻找和消除肿瘤细胞,但在某些情况下也可以使用供体免疫细胞。在这里,我们专注于基于 T 淋巴细胞(T 细胞)的癌症免疫疗法,这些疗法在最初发现移植物抗肿瘤反应是由 T 细胞介导后引起了广泛关注。对 T 细胞发育和功能的认识不断积累,加上遗传学和数据科学的进步,使得使用患者自身(自体)T 细胞进行 ACT(TIL ACT)成为可能。在 TIL ACT 中,从切除的肿瘤组织中收集浸润性淋巴细胞(TIL),进行增强和扩增,然后作为治疗剂回输给患者。已经证明 TIL ACT 可引起多种癌症(包括黑色素瘤、宫颈鳞状细胞癌和胆管癌)的肿瘤客观消退。在这篇综述中,我们简要介绍了 TIL ACT 的历史,并讨论了 TIL ACT 在实体瘤中的临床开发现状。我们还讨论了 TIL ACT 在当前癌症治疗领域的利基以及患者选择的潜在策略。