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:Advances and obstacles of T cell-based immunotherapy in gynecological malignancies.
T细胞介导的免疫疗法通过实现对恶性细胞的精准免疫反应,彻底改变了肿瘤学。
T 细胞介导的免疫治疗通过实现对恶性细胞的精准免疫应答,彻底改变了肿瘤学。嵌合抗原受体(CAR)T 细胞疗法通过基因重编程 T 淋巴细胞以识别肿瘤特异性抗原,已在血液系统恶性肿瘤中显示出临床成功,并正在拓展其在实体瘤中的潜力。妇科癌症,包括卵巢癌、宫颈癌和子宫内膜癌,由于其侵袭性复发模式以及晚期疾病阶段对常规治疗反应有限,持续构成治疗挑战。本综述对 CAR-T 细胞疗法在妇科肿瘤学中的进展进行了全面分析,探讨了肿瘤-免疫相互作用的基本生物学机制、靶抗原验证的临床进展,以及应对免疫抑制性肿瘤微环境的创新策略。讨论了这些恶性肿瘤特有的关键挑战,例如子宫内膜肿瘤的分子异质性、卵巢癌(OC)中腹水介导的 T 细胞功能障碍,以及 HPV 驱动的宫颈癌中病毒抗原动态变化。近期临床证据表明,通过优化 CAR 结构和预处理方案,治疗结局得到改善,客观缓解率在连续几代临床试验中呈现逐步提升。讨论涉及关于治疗持久性和生产一致性方面持续存在的局限性,同时探索了新兴解决方案,如合成生物学方法和多组学指导的抗原选择。通过将临床前见解与转化临床数据相结合,本研究为推进妇科肿瘤中的过继性T细胞疗法建立了一个战略框架,强调将CAR-T技术与个性化新抗原疫苗及微环境重编程药物相结合的协同潜力。这些集体进展凸显了工程化T细胞免疫疗法的变革前景,同时提供了可操作的策略,以克服女性生殖道恶性肿瘤固有的独特生物学障碍。
T cell-mediated immunotherapy has revolutionized oncology by enabling precision immune responses against malignant cells. Chimeric Antigen Receptor (CAR) T-cell therapy, which involves genetically reprogramming T lymphocytes to recognize tumor-specific antigens, has shown clinical success in hematologic malignancies and is expanding its potential in solid tumors. Gynecological cancers, including ovarian, cervical, and endometrial carcinomas, present persistent therapeutic challenges due to their aggressive recurrence patterns and limited responses to conventional therapies in advanced disease stages. This review offers a comprehensive analysis of CAR-T cell therapy advancements in gynecologic oncology, examining fundamental biological mechanisms of tumor-immune interactions, clinical progress in target antigen validation, and innovative approaches to counter immunosuppressive tumor microenvironments. Key challenges specific to these malignancies are discussed, such as molecular heterogeneity in endometrial tumors, ascites-mediated T-cell dysfunction in ovarian cancer (OC), and viral antigen dynamics in HPV- driven cervical carcinomas. Recent clinical evidence shows improved therapeutic outcomes through optimized CAR architectures and preconditioning regimens, with objective response rates demonstrating progressive enhancement across successive clinical trial generations. The discussion addresses ongoing limitations regarding treatment durability and manufacturing consistency while exploring emerging solutions such as synthetic biology approaches and multi-omics guided antigen selection. By integrating preclinical insights with translational clinical data, this work establishes a strategic framework for advancing adoptive T-cell therapies in gynecologic oncology, emphasizing the synergistic potential of combining CAR-T technology with personalized neoantigen vaccines and microenvironment-reprogramming agents. These collective advances underscore the transformative prospects of engineered T-cell immunotherapies while providing actionable strategies to overcome the unique biological barriers inherent to female reproductive tract malignancies.
MEMBER ACCOUNT
登录成功会直接打开下一页。