肿瘤细胞治疗研究
英文原题：Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7.
这些数据表明，nfP2X7 适合作为免疫治疗靶点，因为其在人类肿瘤上广泛表达。
嵌合抗原受体（CAR）T 细胞免疫疗法是一种新型治疗方法，通过基因工程改造患者自身 T 细胞，使其靶向并杀伤恶性细胞。然而，在多种实体瘤中识别肿瘤特异性抗原仍是一项主要挑战。P2X 嘌呤能受体 7（P2X7）是一种细胞表面 ATP 门控阳离子通道；在多种组织来源的癌细胞上发现了一种功能异常的 P2X7 形式，称为 nfP2X7，而健康细胞上检测不到该形式。本文介绍一种靶向 nfP2X7 的原型人源 CAR-T 构建体，其对 12 种实体瘤（乳腺癌、前列腺癌、肺癌、结直肠癌、脑癌和皮肤癌）显示出潜在的抗原特异性细胞毒作用。在乳腺癌和前列腺癌异种移植小鼠模型中，靶向 nfP2X7 的 CAR-T 细胞表现出强效抗肿瘤疗效。这些数据表明，nfP2X7 在多种人类肿瘤中广泛表达，是适宜的免疫治疗靶点。靶向 nfP2X7 的 CAR-T 细胞有望成为治疗人类实体瘤的广谱癌症免疫疗法。
Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients' own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types, remains a major challenge. P2X purinoceptor 7 (P2X7) is a cell surface expressed ATP gated cation channel, and a dysfunctional version of P2X7, named nfP2X7, has been identified on cancer cells from multiple tissues, while being undetectable on healthy cells. We present a prototype -human CAR-T construct targeting nfP2X7 showing potential antigen-specific cytotoxicity against twelve solid cancer types (breast, prostate, lung, colorectal, brain and skin). In xenograft mouse models of breast and prostate cancer, CAR-T cells targeting nfP2X7 exhibit robust anti-tumour efficacy. These data indicate that nfP2X7 is a suitable immunotherapy target because of its broad expression on human tumours. CAR-T cells targeting nfP2X7 have potential as a wide-spectrum cancer immunotherapy for solid tumours in humans.
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