← 返回前沿论文

胃癌免疫治疗的现状与挑战:聚焦 CAR-T 细胞治疗策略

英文原题:Current progress and challenges of immunotherapy in gastric cancer: A focus on CAR-T cells therapeutic approach.

查看英文原题

Current progress and challenges of immunotherapy in gastric cancer: A focus on CAR-T cells therapeutic approach.

PubMed 2023/01/30(内容时间) Life Sci Q1 · IF 6.4(JCR 2025)

研究概要

胃癌 (GC) 是一种严重的恶性肿瘤,是全球第三大常见癌症死因。

中文摘要

胃癌(GC)是一种严重恶性肿瘤,是全球第三大癌症死亡原因。尽管放化疗有所发展,接受此类治疗的GC患者并未获得充分的生存获益。GC免疫原性受到高度免疫抑制性微环境的限制;因此,进一步了解GC分子生物学,有望促成包括特异性免疫疗法在内的新治疗策略。目前免疫疗法主要包括细胞因子、免疫检查点、单克隆抗体(mAb)、双特异性抗体(BisAb)、抗体药物偶联物(ADC)和嵌合抗原受体(CAR)。免疫疗法治疗GC已取得显著进展;研究显示,程序性死亡蛋白1(PD1)抑制剂纳武利尤单抗作为GC三线治疗具有适当的安全性和疗效。雷莫芦单抗和claudiximab等多种单克隆抗体治疗GC有效,尤其与其他疗法联合时。尽管CAR疗法治疗实体瘤仍面临挑战,但其靶点覆盖多种GC细胞相关靶标;其中,靶向细胞间黏附分子(ICAM)-1和CLDN18.2的CAR-T细胞已显示有希望的结果。尽管上述疗法的反应令人鼓舞,部分反应也具有持久性,但并非所有患者均能获益。本综述介绍多种免疫疗法(尤其是CAR-T细胞疗法)的发展、当前应用、GC临床数据及其局限。

展开英文摘要原文

Gastric cancer (GC) is a severe malignancy, accounting for the third most common cancer death worldwide. Despite the development of chemo-radiation therapy, there has not been sufficient survival advantage in patients with GC who were treated by these methods. GC immunogenicity is hampered by a highly immunosuppressive microenvironment; therefore, further understanding of the molecular biology of GC is the potential to achieve new therapeutic strategies in GC therapy, including specific immunotherapy. Current immunotherapies are mainly based on cytokines, immune checkpoints, monoclonal antibodies (mAb), bispecific antibodies (BisAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR). Immunotherapy has made significant progress in the treatment of GC, so that studies show that nivolumab as a programmed death 1 (PD1) inhibitor has proper safety and effectiveness as a third-line treatment for GC patients. Multiple monoclonal antibodies like ramucirumab and claudiximab were effective in treating GC patients, especially in combination with other treatments. Despite the challenges of CAR therapy in solid tumors, CAR therapy targets various GC cells targets; among them, intercellular adhesion molecule (ICAM)-1 CAR-T cell and CLDN18.2 CAR-T cell have shown promising results. Although responses to all these treatments are encouraging and in some cases, durable, these successes are not seen in all treated patients. The present review represents the development of various immunotherapies especially CAR-T cell therapy, its current use, clinical data in GC, and their limitations.

论文信息

作者
Entezam M、Sanaei MJ、Mirzaei Y、Mer AH、Abdollahpour-Alitappeh M、Azadegan-Dehkordi F、Bagheri N
第一作者单位
Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran; Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.Iran
通讯作者单位
Department of Microbiology and Immunology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: n.bagheri1985@gmail.com.Iran
文献类型
综述
期刊
Life sciences2023 Apr 1
原文标识
PubMed 36720453 · DOI 10.1016/j.lfs.2023.121459