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:Rewiring the immune response in lung cancer: current progress in bispecific antibodies, CAR-T therapy, and the rise of in vivo CAR-T platforms.
肺癌仍是全球癌症死亡的首要原因,并持续造成沉重的临床负担,尤其是在晚期非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)中。
肺癌仍是全球癌症死亡的首要原因,持续造成沉重的临床负担,尤其是晚期非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)。靶向治疗、抗血管生成药物、免疫检查点抑制剂和抗体药物偶联物虽改善了部分患者的结局,但原发性和获得性耐药仍限制疗效持久性。本综述全面回顾肺癌免疫治疗策略的近期进展,重点讨论双特异性抗体、嵌合抗原受体(CAR)T 细胞治疗及新兴的体内 CAR 工程技术,并阐述其临床依据、最新转化研究和早期临床证据,以及靶向毒性、脱靶组织毒性、细胞因子释放综合征、T 细胞持续性有限、肿瘤归巢不足和肿瘤微环境免疫抑制等关键挑战。总体而言,双特异性抗体目前在肺癌中显示出较好的疗效和安全性;CAR 设计及体内递送的进展则可能拓宽 CAR-T 治疗在这一疾病中的应用。
Lung cancer remains the leading cause of cancer mortality worldwide and continues to impose a major clinical burden, particularly in advanced non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although targeted therapies, antiangiogenic agents, immune checkpoint inhibitors, and antibody-drug conjugates have improved outcomes in selected patients, durable responses remain limited by primary and acquired resistance. Here, we comprehensively review recent progress in immunologically oriented therapeutic strategies for lung cancer, focusing on bispecific antibodies, chimeric antigen receptor (CAR) T-cell therapy, and emerging in vivo CAR-engineering modalities. We further elaborate on the clinical rationale, latest translational and early clinical evidence, and key challenges, including on-target, off-tumor toxicity, cytokine release syndrome, limited T-cell persistence, insufficient tumor trafficking, and immunosuppression within the tumor microenvironment. Taken together, we find that while bispecific antibodies currently show favorable efficacy and safety in lung cancer; advances in CAR design and in vivo delivery may broaden the applicability of CAR-T therapy in this setting.
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