Identification of cancer-specific cell surface targets for CAR-T cell therapy.

Naoki Hosen
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Abstract

One should identify appropriate cell surface targets to develop new CAR-T cells. Currently, lineage-specific antigens such as CD19 or B cell maturation antigen (BCMA) are being used as targets for CAR-T cells. However, in most cancers, lineage-specific antigens cannot be used as targets because targeting normal counterparts expressing them causes fatal toxicity. Cancer-specific transcripts have been extensively searched for using transcriptome analysis, but only a few candidates were reported. We have been working on identifying tumor-specific antigen structures, for example constitutively activated conformer of integrin b7 in multiple myeloma. Recently, several researchers have been working on a logic gate system that can react only when two antigens are expressed on the cell surface.

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为 CAR-T 细胞疗法鉴定癌症特异性细胞表面靶点。
开发新的 CAR-T 细胞应确定适当的细胞表面靶点。目前,CD19 或 B 细胞成熟抗原(BCMA)等细胞系特异性抗原被用作 CAR-T 细胞的靶点。然而,在大多数癌症中,细胞系特异性抗原不能用作靶点,因为靶向表达这些抗原的正常对应物会导致致命毒性。癌症特异性转录本已通过转录组分析被广泛搜索,但只有少数候选者被报道。我们一直致力于确定肿瘤特异性抗原结构,例如多发性骨髓瘤中整合素 b7 的构象激活构象。最近,几位研究人员正在研究一种逻辑门系统,该系统只有在细胞表面表达两种抗原时才会发生反应。
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