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.

中文翻译：

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绘制癌症表面蛋白质组图谱以寻找免疫治疗的靶抗原


基于免疫的治疗干预识别位于癌细胞细胞表面的蛋白质，正在成为一种有前途的癌症治疗方法。基于抗体的疗法和工程化 T 细胞现已获得美国食品和药物管理局 (FDA) 的批准，可用于治疗某些恶性肿瘤。这些疗法利用癌细胞上高表达的一些细胞表面蛋白来释放限制抗肿瘤反应的免疫激活的负调节（例如，PD-1、PD-L1、CTLA4）或将T细胞特异性重定向到血癌细胞。例如，CD19 和 B 细胞成熟抗原）。阻碍这些新型治疗策略更广泛地应用于所有癌症类型的一个限制是缺乏适合所有适应症的靶抗原，部分原因是识别此类靶标的挑战。理想的靶抗原是在恶性细胞上高表达而在健康组织中不存在的细胞表面蛋白。质谱、富集方案以及用于细胞表面蛋白分离和注释的计算工具方面的技术进步最近使得能够对癌细胞表面蛋白质组进行全面分析，从中可能出现新的免疫治疗靶抗原。在此，我们回顾一下该领域的最新进展。