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:Mapping the cancer surface proteome in search of target antigens for immunotherapy.
Mapping the cancer surface proteome in search of target antigens for immunotherapy.
识别癌细胞表面定位蛋白的免疫治疗干预正逐渐成为一种有前景的癌症治疗方法。
基于识别癌细胞表面定位蛋白的免疫治疗干预正逐渐成为一种有前景的癌症治疗方法。基于抗体的疗法和工程化T细胞现已获得美国食品药品监督管理局批准用于治疗某些恶性肿瘤。这些疗法利用少数在癌细胞上高表达的细胞表面蛋白来解除限制抗肿瘤反应的免疫激活负调控(如PD-1、PD-L1、CTLA4),或将T细胞特异性重定向至血液癌细胞(如CD19和B细胞成熟抗原)。阻碍这些新型治疗策略更广泛应用至所有癌症类型的一个限制因素是缺乏适用于所有适应症的合适靶抗原,部分原因在于识别此类靶标存在挑战。理想的靶抗原是在恶性细胞上高表达而在健康组织中缺失的细胞表面蛋白。质谱技术、富集方案以及用于细胞表面蛋白分离和注释的计算工具的进步,最近使得对癌细胞表面蛋白质组的全面分析成为可能,从中可能发现新型免疫治疗靶抗原。在此,我们综述该领域的最新进展。
Immune-based therapeutic interventions recognizing proteins localized on the cell surface of cancer cells are emerging as a promising cancer treatment. Antibody-based therapies and engineered T cells are now approved by the Food and Drug Administration to treat some malignancies. These therapies utilize a few cell surface proteins highly expressed on cancer cells to release the negative regulation of immune activation that limits antitumor responses (e.g., PD-1, PD-L1, CTLA4) or to redirect the T cell specificity toward blood cancer cells (e.g., CD19 and B cell maturation antigen). One limitation preventing broader application of these novel therapeutic strategies to all cancer types is the lack of suitable target antigens for all indications owing in part to the challenges in identifying such targets. Ideal target antigens are cell surface proteins highly expressed on malignant cells and absent in healthy tissues. Technological advances in mass spectrometry, enrichment protocols, and computational tools for cell surface protein isolation and annotation have recently enabled comprehensive analyses of the cancer cell surface proteome, from which novel immunotherapeutic target antigens may emerge. Here, we review the most recent progress in this field.
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