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MSLN(间皮素)、ANTXR1(TEM8)和 MUC3A 是胃腺癌 CAR T 细胞治疗的有效抗原靶点。

MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma.

机构信息

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Digestive Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Cell Biochem. 2019 Apr;120(4):5010-5017. doi: 10.1002/jcb.27776. Epub 2018 Sep 27.

Abstract

Gastric adenocarcinoma is usually diagnosed in late stages, necessitating the use of different therapeutic modalities. Currently, antibody-based therapies have also been approved through with limited clinical efficacy. Reinforcing antibody-based immunotherapy by using chimeric antigen receptor (CAR) T cells may enhance the approach. However, the cells can cause severe on-target and off-tumor toxicities owing to their higher sensitivity to low-level antigen expressions. To address the need for safe and reliable targets, we made a bioinformatics pipeline by which we screened overexpressed genes in the disease for off-tumor sites in many normal tissues. Our inspection showed that MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the probable targets of CAR T cell therapy in gastric adenocarcinoma. The proposed antigenic targets might respond to the need to simultaneously target multiple antigens in a tumor matrix to prevent resistance.

摘要

胃腺癌通常在晚期诊断,需要采用不同的治疗方法。目前,抗体药物治疗也已获得批准,但临床疗效有限。通过嵌合抗原受体 (CAR) T 细胞增强抗体免疫疗法可能会提高疗效。然而,由于 CAR T 细胞对低水平抗原表达具有更高的敏感性,它们可能会导致严重的靶内和靶外毒性。为了解决安全可靠靶点的需求,我们通过生物信息学管道筛选了疾病中在许多正常组织中过表达的基因,作为肿瘤外靶点。我们的检查表明,MSLN(间皮素)、ANTXR1(TEM8)和 MUC3A 可能是胃腺癌 CAR T 细胞治疗的潜在靶点。这些拟议的抗原靶点可能符合同时针对肿瘤基质中多个抗原的需求,以防止耐药性的产生。

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