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:Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout.
过继性细胞治疗(ACT)在肉瘤中已显示出令人鼓舞的结果,afami-cel 在滑膜肉瘤中实现了持久缓解,针对 NY-ESO-1 和 MAGE-A4 的早期 TCR-T 试验也显示出有意义的缓解率。
背景:2024年9月,第二届肉瘤科学战略进展(SASS)年会在美国国立卫生研究院召开。来自全国的肉瘤专家围绕肉瘤生物学和临床照护中的临床前研究、临床试验、机遇、挑战及未来方向进行讨论,重点关注免疫治疗。肉瘤免疫学分组专门讨论了过继细胞疗法(ACT)当前及未来在肉瘤中的应用。本文总结相关讨论,为研究人员和临床医生提供综合参考。结果:ACT在肉瘤中显示出令人鼓舞的结果,例如afami-cel在滑膜肉瘤中取得持久应答,针对NY-ESO-1和MAGE-A4的早期TCR-T试验也显示出有意义的应答率。要在此基础上进一步发展,需要发现新靶点、选择最佳细胞类型、优化预处理方案、与酪氨酸激酶抑制剂(TKI)等其他治疗策略联合,并利用基于深入肿瘤微环境认识而开发的预测性生物标志物。结论:afami-cel治疗滑膜肉瘤的成功表明肉瘤是ACT有前景的靶病种;但要扩大其影响,需要发现新靶点、优化细胞选择和预处理方案、采用联合治疗、深化对肿瘤微环境的认识,并开发预测性生物标志物,从而使更多患者获得更持久的应答。
BACKGROUND: In September of 2024, the 2nd annual meeting of the Strategic Advances in Sarcoma Science (SASS) convened at the National Institutes of Health. This gathering of national sarcoma experts focused on preclinical studies, clinical trials, opportunities, challenges, and future directions in sarcoma biology and clinical care with a focus on immunotherapy. The Immunology in Sarcoma breakout group conducted a dedicated discussion focused on the current and future implementation of adoptive cellular therapies (ACTs) in sarcomas. The current manuscript summarizes these discussions and provides a comprehensive resource for researchers and clinicians. RESULTS: Adoptive cell therapy (ACT) has shown encouraging results in sarcomas with afami-cel achieving durable responses in synovial sarcoma and early TCR-T trials against NY-ESO-1 and MAGE-A4 demonstrating meaningful response rates. Building on these outcomes will require discovering new targets, selecting optimal cell types, refining conditioning regimens, combining with alternative treatment strategies such as TKIs, and leveraging predictive biomarkers informed by a deeper understanding of the tumor microenvironment. CONCLUSIONS: Sarcomas are promising targets for adoptive cell therapy (ACT), as shown by afami-cel's success in synovial sarcoma, but broader impact requires new target discovery, optimal cell selection, improved conditioning, combination treatments, deeper tumor microenvironment understanding, and predictive biomarkers to achieve more durable responses for more patients.
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