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:Novel approaches to modulate CAR-T cell function by targeting the tumor microenvironment in ovarian cancer.
晚期疾病约 30% 的五年生存率之低,凸显了亟需创新的治疗策略。
尽管常规治疗不断进步,卵巢癌(OC)仍是致死率最高的妇科恶性肿瘤之一,晚期患者约30%的五年生存率凸显了开发创新治疗策略的迫切需求。CAR-T(CAR-T)细胞疗法已革新血液系统恶性肿瘤治疗,但应用于卵巢癌复杂的免疫抑制性肿瘤微环境(TME)时仍面临重大挑战。本综述全面探讨关键研究问题:卵巢癌TME中的细胞和分子组分在多大程度上抑制CAR-T细胞细胞毒功能,以及哪些信号模式与CAR-T浸润肿瘤或在肿瘤团块内持久存留减少相关。我们系统考察卵巢癌TME的多方面免疫抑制机制,并评估克服这些屏障的突破性策略,包括新一代CAR工程化、联合治疗方法及创新TME调节技术。本文提出的认识为CAR-T疗法从有前景的概念转化为卵巢癌临床治疗提供了关键路线图,有望改善这一顽固恶性肿瘤患者的结局;该疾病迫切需要创新治疗选择。
Ovarian cancer (OC) remains one of the most lethal gynecological malignancies despite advances in conventional therapeutic approaches. The dismal approximately 30% five-year survival rate for advanced disease highlight the urgent need for innovative treatment strategies. Chimeric antigen receptor T (CAR-T) cell therapy, having revolutionized treatment paradigms in hematological malignancies, faces significant challenges when applied to the complex immunosuppressive tumor microenvironment (TME) of ovarian cancer. This comprehensive review investigates critical research questions regarding the extent to which cellular and molecular components of the ovarian cancer TME inhibit CAR-T cell cytotoxic function, and the signaling patterns associated with reduced CAR-T cell infiltration or persistence in tumor masses. We systematically examine the multifaceted immunosuppressive mechanisms within the ovarian cancer TME and evaluate breakthrough strategies designed to overcome these barriers, including next-generation CAR engineering, combinatorial therapeutic approaches, and innovative TME-modulating technologies. The insights presented here provide a crucial roadmap for translating CAR-T therapy from promising concept to clinical reality in ovarian cancer treatment, potentially transforming outcomes for patients with this recalcitrant malignancy where innovative therapeutic options are urgently needed.
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