Department of Urology, CHA University College of Medicine, CHA Bundang Medical Center, Seongnam, Korea.
Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Investig Clin Urol. 2022 Sep;63(5):486-498. doi: 10.4111/icu.20220103.
In the clinical setting of renal cell carcinoma (RCC), immune reactions such as tumor-specific T cell responses can be spontaneous events or can be elicited by checkpoint inhibitors, cytokines, and other immunotherapy modalities. The results from immunotherapy have led to significant advances in treatment methods and patient outcomes. The approval of nivolumab primarily as a second-line monotherapy and the latest approval of novel combination therapies as first-line treatment have established the significance of immunotherapy in the treatment of RCC. In this perspective, chimeric antigen receptor (CAR)-T cell therapy represents a major advance in the developing field of immunotherapy. This treatment modality facilitates T cells to express specific CARs on the cell surface which are reinfused to the patient to treat the analogous tumor cells. After showing treatment potential in hematological malignancies, this new therapeutic approach has become a strong candidate as a therapeutic modality for solid neoplasms. Although CAR-T cell therapy has shown promise and clinical benefit compared to previous T-cell modulated immunotherapies, further studies are warranted to overcome unfavorable physiological settings and hindrances such as the lack of specific molecular targets, depletion of CAR-T cells, a hostile tumor microenvironment, and on/off-tumor toxicities. Several approaches are being considered and research is ongoing to overcome these problems. In this comprehensive review, we provide the rationale and preliminary results of CAR-T cell therapy in RCC and discuss emerging novel strategies and future directions.
在肾细胞癌 (RCC) 的临床环境中，免疫反应（如肿瘤特异性 T 细胞反应）可以是自发事件，也可以通过检查点抑制剂、细胞因子和其他免疫疗法诱发。免疫疗法的结果导致治疗方法和患者预后的重大进展。纳武利尤单抗最初作为二线单药治疗的批准，以及新型联合治疗方案作为一线治疗的最新批准，确立了免疫疗法在 RCC 治疗中的重要地位。在这种观点下，嵌合抗原受体 (CAR)-T 细胞疗法代表了免疫治疗领域发展的重大进展。这种治疗方式使 T 细胞能够在细胞表面表达特定的 CAR，然后将这些 CAR 重新输注到患者体内以治疗类似的肿瘤细胞。在血液恶性肿瘤中显示出治疗潜力后，这种新的治疗方法已成为治疗实体瘤的一种强有力候选方法。尽管 CAR-T 细胞疗法与以前的 T 细胞调节免疫疗法相比显示出了治疗潜力和临床获益，但仍需要进一步的研究来克服不利的生理环境和障碍，如缺乏特异性分子靶点、CAR-T 细胞耗竭、肿瘤微环境恶劣以及肿瘤内外毒性。正在考虑几种方法，并且正在进行研究以克服这些问题。在这篇全面的综述中，我们提供了 CAR-T 细胞疗法在 RCC 中的原理和初步结果，并讨论了新兴的新型策略和未来方向。
