下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Toward a comprehensive solution for treating solid tumors using T-cell receptor therapy: A review.
T细胞受体疗法(TCR-T)已在某些实体瘤(如人乳头瘤病毒相关肿瘤、滑膜肉瘤和黑色素瘤)中展现出疗效、持久性和安全性优势。
T细胞受体疗法(TCR-T)已在某些实体瘤(如人乳头瘤病毒相关肿瘤、滑膜肉瘤和黑色素瘤)中展现出疗效、持久性和安全性优势。本研究旨在为开发针对实体瘤的TCR-T提供审慎的考量。因此,在本综述中,我们总结了TCR-T目前的临床应用、其模式的优越性,并探讨了与实体瘤疗效/安全性相关的参数,特别是亲和力、药代动力学/药效动力学和适应症。此外,我们研究了与亲和力相关的关键因素,包括抗原选择、T细胞受体获取、优化和共受体结合。而且,我们基于当前的RNA-seq数据集,重新审视了肿瘤抗原的表达,以期获得对实体瘤潜在更高的覆盖率。最后,我们讨论了TCR-T目前的局限性和未来方向。
T-cell receptor therapy (TCR-T) has demonstrated efficacy, durability, and safety advantages in certain solid tumors (such as human papillomavirus-related tumors, synovial sarcoma, and melanoma). This study aimed to provide careful considerations for developing TCR-T for solid tumors. Therefore, in this review, we have summarized the current clinical application, advantage of TCR-T modalities and explored efficacy/safety-related parameters, particularly avidity, pharmacokinetics/pharmacodynamics, and indications, for solid tumors. Furthermore, we have investigated critical factors related to avidity, including antigen selection, T-cell receptor acquisition, optimization, and co-receptor engagement. Moreover, we have re-examined the expression of tumor antigens for a potentially higher coverage rate of solid tumors based on the current RNA-seq datasets. Finally, we have discussed the current limitations and future directions of TCR-Ts.
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