肿瘤细胞治疗研究
英文原题：Immunotherapy of sarcomas with modified T cells.
Immunotherapy of sarcomas with modified T cells.
大量临床试验正在评估肿瘤特异性CAR-T 细胞和高亲和力T细胞受体（TCR）转导T细胞在肉瘤中的应用。值得注意的是， translocation-dependent 滑膜肉瘤和黏液样/圆细胞脂肪肉瘤是多项II期试验的研究对象，这些试验评估靶向癌睾丸抗原纽约食管鳞状细胞癌-1（NY-ESO-1）和黑色素瘤抗原-A4（MAGE A4）的TCR，在滑膜肉瘤中，针对NY-ESO-1的修饰T细胞观察到高达60%的缓解率。修饰T细胞治疗面临的挑战包括HLA限制性、非免疫原性肿瘤微环境（TME）、激进性淋巴细胞清除和免疫介导的毒性限制细胞因子的共输注。
总结改良T细胞疗法在肉瘤中的发展，并讨论迄今为止已发表和正在进行的相关临床试验。
大量临床试验正在评估肿瘤特异性CAR-T 细胞和高亲和力T细胞受体（TCR）转导T细胞在肉瘤中的应用。值得注意的是， translocation-dependent 滑膜肉瘤和黏液样/圆细胞脂肪肉瘤是多项II期试验的研究对象，这些试验评估靶向癌睾丸抗原纽约食管鳞状细胞癌-1（NY-ESO-1）和黑色素瘤抗原-A4（MAGE A4）的TCR，在滑膜肉瘤中，针对NY-ESO-1的修饰T细胞观察到高达60%的缓解率。修饰T细胞治疗面临的挑战包括HLA限制性、非免疫原性肿瘤微环境（TME）、激进性淋巴细胞清除和免疫介导的毒性限制细胞因子的共输注。摘要：通过递送修饰T细胞来增强适应性免疫反应的细胞治疗是肉瘤新治疗开发的一个领域，其中可以识别出可靠表达的、普遍存在的靶抗原。为了提高修饰TCR的特异性、信号传导、增殖和持久性，并通过安全操控肉瘤TME来增强临床反应，必要的治疗工具将是充分发挥这种方法潜力的关键。
PURPOSE OF REVIEW: To summarize the development of modified T-cell therapies in sarcomas and discuss relevant published and ongoing clinical trials to date. RECENT FINDINGS: Numerous clinical trials are underway evaluating tumor-specific chimeric antigen receptor T cells and high affinity T-cell receptor (TCR)-transduced T cells in sarcomas. Notably, translocation-dependent synovial sarcoma and myxoid/round cell liposarcoma are the subject of several phase II trials evaluating TCRs targeting cancer testis antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen-A4 (MAGE A4), and response rates of up to 60% have been observed for NY-ESO-1 directed, modified T cells in synovial sarcoma. Challenges posed by modified T-cell therapy include limitations conferred by HLA-restriction, non-immunogenic tumor microenvironments (TME), aggressive lymphodepletion and immune-mediated toxicities restricting coinfusion of cytokines. SUMMARY: Cellular therapy to augment the adaptive immune response through delivery of modified T cells is an area of novel therapeutic development in sarcomas where a reliably expressed, ubiquitous target antigen can be identified. Therapeutic tools to improve the specificity, signaling, proliferation and persistence of modified TCRs and augment clinical responses through safe manipulation of the sarcoma TME will be necessary to harness the full potential of this approach.
MEMBER ACCOUNT
登录成功会直接打开下一页。
