T-cell receptor (TCR)-based adoptive therapy employs genetically modified lymphocytes that are directed against specific tumor markers. This therapeutic modality requires a structured and integrated process that involves patient screening (e.g., for HLA-A*02:01 and specific tumor targets), leukapheresis, generation of transduced TCR product, lymphodepletion, and infusion of the TCR-based adoptive therapy. In this review, we summarize the current technology and early clinical development of TCR-based therapy in patients with solid tumors. The challenges of TCR-based therapy include those associated with TCR product manufacturing, patient selection, and preparation with lymphodepletion. Overcoming these challenges, and those posed by the immunosuppressive microenvironment, as well as developing next-generation strategies is essential to improving the efficacy and safety of TCR-based therapies. Optimization of technology to generate TCR product, treatment administration, and patient monitoring for adverse events is needed. The implementation of novel TCR strategies will require expansion of the TCR approach to patients with HLA haplotypes beyond HLA-A*02:01 and the discovery of novel tumor markers that are expressed in more patients and tumor types. Ongoing clinical trials will determine the ultimate role of TCR-based therapy in patients with solid tumors.

中文翻译：

---

基于 T 细胞受体的疗法：实体瘤的创新治疗方法


基于 T 细胞受体 (TCR) 的过继疗法采用针对特定肿瘤标志物的基因改造淋巴细胞。这种治疗方式需要一个结构化和综合的过程，包括患者筛查（例如，HLA-A*02:01 和特定肿瘤靶点）、白细胞去除术、转导 TCR 产品的生成、淋巴细胞清除和基于 TCR 的过继疗法的输注。在这篇综述中，我们总结了实体瘤患者基于 TCR 的治疗的当前技术和早期临床进展。基于 TCR 的治疗面临的挑战包括与 TCR 产品制造、患者选择和淋巴细胞清除准备相关的挑战。克服这些挑战以及免疫抑制微环境带来的挑战，以及开发下一代策略对于提高基于 TCR 的疗法的疗效和安全性至关重要。需要优化生成 TCR 产品、治疗管理和患者不良事件监测的技术。新型 TCR 策略的实施需要将 TCR 方法扩展到 HLA-A*02:01 以外的 HLA 单倍型患者，并发现在更多患者和肿瘤类型中表达的新型肿瘤标志物。正在进行的临床试验将确定基于 TCR 的治疗对实体瘤患者的最终作用。