决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Cellular Immunotherapy for Cervical Cancer: Next Therapeutics Frontiers.
我们得出结论,该领域的未来在于合理的联合策略(例如,与免疫检查点阻断联合)和下一代工程改造(例如,装甲CAR、逻辑门、异体平台),以克服生产复杂性、毒性和高成本。
宫颈癌,尤其是其晚期阶段,需要新的治疗范式。细胞免疫治疗利用HPV E6/E7癌蛋白的组成性表达作为近乎理想的肿瘤特异性抗原。本综述系统评估了正在研究中的四种主要平台:TIL(肿瘤浸润淋巴细胞)、TCR工程化T细胞、CAR-T细胞和CAR-NK细胞。我们批判性分析了每种模式的临床前理论基础、临床试验格局、安全性考量及生产挑战。TIL疗法已实现持久的完全缓解并获得FDA突破性疗法认定。TCR-T细胞能够精准靶向细胞内病毒表位,但受HLA限制。CAR-T细胞提供强效、MHC非依赖性识别,但面临靶向/脱靶毒性和抑制性肿瘤微环境。CAR-NK细胞具有有利的安全性特征和现货型潜力。我们得出结论,该领域的未来在于合理的联合策略(例如,与免疫检查点阻断联合)和下一代工程化改造(例如,装甲CAR、逻辑门、异体平台),以克服生产复杂性、毒性和高成本。克服这些障碍对于将这些疗法扩展到宫颈癌负担最高的资源有限地区至关重要。
Cervical cancer, particularly its advanced stages, requires novel therapeutic paradigms. Cellular immunotherapy exploits the constitutive expression of HPV E6/E7 oncoproteins as near-ideal tumor-specific antigens. This review systematically evaluates four principal platforms under investigation: tumor-infiltrating lymphocytes (TILs), TCR-engineered T cells, CAR-T cells, and CAR-NK cells. We critically analyze the preclinical rationale, clinical trial landscape, safety considerations, and manufacturing challenges for each modality. TIL therapy has achieved durable complete responses and an FDA Breakthrough Therapy designation. TCR-T cells enable precise targeting of intracellular viral epitopes but are HLA-restricted. CAR-T cells offer potent, MHC-independent recognition, yet face on-target/off-tumor toxicity and a suppressive tumor microenvironment. CAR-NK cells present a favorable safety profile and off-the-shelf potential. We conclude that the future of this field lies in rational combination strategies (e.g., with immune checkpoint blockade) and next-generation engineering (e.g., armored CARs, logic gates, allogeneic platforms) to overcome manufacturing complexity, toxicity, and high costs. Overcoming these barriers is essential to extend these therapies to resource-limited settings where the burden of cervical cancer is highest.
MEMBER ACCOUNT
登录成功会直接打开下一页。