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:Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy.
Claudin18.2(CLDN18.2)是紧密连接蛋白家族成员 claudin18 的一种亚型,是高度选择性的生物标志物,在正常组织中表达有限,但在胃癌/胃食管结合部癌(GC/GEJ)、乳腺癌、结肠癌、肝癌、头颈癌、支气管癌和非小细胞肺癌等多种原发性恶性肿瘤的发生发展过程中常出现异常表达。CLDN18.2 参与肿瘤细胞增殖、分化和迁移。近期研究发现,CLDN18.2 表达可能是这些肿瘤诊断和治疗的特异性标志物。凭借其特异性表达模式,CLDN18.2 已成为多种癌症(尤其是 GC)的独特靶向治疗分子;例如,研究者已开发靶向 CLDN18.2 的单克隆抗体 zolbetuximab(claudiximab,IMAB362)。本文综述靶向 CLDN18.2 的免疫治疗策略研发最新进展,包括单克隆抗体、双特异性抗体、重定向靶向 CLDN18.2 的 CAR-T 细胞,以及抗体药物偶联物。
The claudin18.2 (CLDN18.2) protein, an isoform of claudin18, a member of the tight junction protein family, is a highly selective biomarker with limited expression in normal tissues and often abnormal expression during the occurrence and development of various primary malignant tumors, such as gastric cancer/gastroesophageal junction (GC/GEJ) cancer, breast cancer, colon cancer, liver cancer, head and neck cancer, bronchial cancer and non-small-cell lung cancer. CLDN18.2 participates in the proliferation, differentiation and migration of tumor cells. Recent studies have identified CLDN18.2 expression as a potential specific marker for the diagnosis and treatment of these tumors. With its specific expression pattern, CLDN18.2 has become a unique molecule for targeted therapy in different cancers, especially in GC; for example, agents such as zolbetuximab (claudiximab, IMAB362), a monoclonal antibody (mAb) against CLDN18.2, have been developed. In this review, we outline recent advances in the development of immunotherapy strategies targeting CLDN18.2, including monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), chimeric antigen receptor T (CAR-T) cells redirected to target CLDN18.2, and antibody-drug conjugates (ADCs).
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