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:The Role of Mesothelin in Gynecological Tumors and Its Significance in Targeted Therapies-A Review.
间皮素(MSLN)是一种细胞表面糖蛋白,在正常组织中表达有限,但在包括妇科恶性肿瘤在内的实体瘤中频繁过表达。
间皮素(MSLN)是一种细胞表面糖蛋白,在正常组织中的表达有限,但在包括妇科恶性肿瘤在内的实体瘤中常过表达。本综述总结MSLN在卵巢癌、子宫内膜癌和宫颈癌中的生物学作用、诊断价值、预后意义及治疗潜力。临床和实验研究证据表明,MSLN可通过与CA125相互作用、促进细胞黏附及腹膜转移、激活致癌信号通路、调节免疫反应及促成化疗耐药,推动肿瘤进展。MSLN高表达与疾病临床分期较晚、铂类耐药和较差生存结局相关,尤其是在卵巢癌患者中,但其预后研究结果尚不一致。循环可溶性MSLN可作为微创生物标志物,与已确立标志物联合时可能提高诊断准确性。靶向MSLN的治疗策略包括抗体-药物偶联物、CAR-T及NK细胞疗法、单克隆抗体、免疫毒素、疫苗和免疫检查点阻断,在临床前及早期临床研究中显示出前景,尤其适用于耐药或复发疾病。总体而言,MSLN是妇科癌症精准肿瘤学中有前景的靶点,但仍需进一步临床研究验证其诊断用途并优化靶向治疗方案。
Mesothelin (MSLN) is a cell surface glycoprotein with limited expression in normal tissues but frequent overexpression in solid tumors, including gynecological malignancies. This review summarizes the state of the art on the biological role, diagnostic value, prognostic significance, and therapeutic potential of MSLN in ovarian, endometrial, and cervical cancers. Evidence from clinical and experimental studies indicates that MSLN contributes to tumor progression through interactions with CA125, promotion of cell adhesion and peritoneal metastasis, activation of oncogenic signaling pathways, modulation of immune responses, and development of chemoresistance. Elevated MSLN expression has been associated with advanced clinical stage of the disease, platinum resistance, and poorer survival outcomes, particularly in ovarian cancer patients, although prognostic findings remain inconsistent. Circulating soluble MSLN may serve as a minimally invasive biomarker and may improve diagnostic accuracy when combined with established markers. Therapeutic MSLN strategies-antibody-drug conjugates, CAR-T and NK cell therapies, monoclonal antibodies, immunotoxins, vaccines, and checkpoint blockade-provide promising pre-clinical and early clinical results, particularly in resistant or recurrent forms of the disease. Overall, MSLN constitutes a promising target for precision oncology in gynecological cancers, although further clinical studies are required to validate its diagnostic utility and optimize targeted therapeutic approaches.
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