Zhu Yu-Ge, Xiao Bu-Fan, Zhang Jing-Tao, Cui Xin-Run, Lu Zhe-Ming, Wu Nan
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Front Oncol. 2021 Nov 9;11:763806. doi: 10.3389/fonc.2021.763806. eCollection 2021.
Esophageal cancer is an exceedingly aggressive and malignant cancer that imposes a substantial burden on patients and their families. It is usually treated with surgery, chemotherapy, radiotherapy, and molecular-targeted therapy. Immunotherapy is a novel treatment modality for esophageal cancer wherein genetically engineered adoptive cell therapy is utilized, which modifies immune cells to attack cancer cells. Using chimeric antigen receptor (CAR) or T cell receptor (TCR) modified T cells yielded demonstrably encouraging efficacy in patients. CAR-T cell therapy has shown robust clinical results for malignant hematological diseases, particularly in B cell-derived malignancies. Natural killer (NK) cells could serve as another reliable and safe CAR engineering platform, and CAR-NK cell therapy could be a more generalized approach for cancer immunotherapy because NK cells are histocompatibility-independent. TCR-T cells can detect a broad range of targeted antigens within subcellular compartments and hold great potential for use in cancer therapy. Numerous studies have been conducted to evaluate the efficacy and feasibility of CAR and TCR based adoptive cell therapies (ACT). A comprehensive understanding of genetically-modified T cell technologies can facilitate the clinical translation of these adoptive cell-based immunotherapies. Here, we systematically review the state-of-the-art knowledge on genetically-modified T-cell therapy and provide a summary of preclinical and clinical trials of CAR and TCR-transgenic ACT.
食管癌是一种极具侵袭性和恶性的癌症,给患者及其家庭带来了沉重负担。它通常采用手术、化疗、放疗和分子靶向治疗。免疫疗法是一种针对食管癌的新型治疗方式,其中利用了基因工程过继性细胞疗法,该疗法对免疫细胞进行改造以攻击癌细胞。使用嵌合抗原受体(CAR)或T细胞受体(TCR)修饰的T细胞在患者中产生了明显令人鼓舞的疗效。CAR-T细胞疗法已在恶性血液疾病中显示出强大的临床效果,尤其是在B细胞来源的恶性肿瘤中。自然杀伤(NK)细胞可作为另一个可靠且安全的CAR工程平台,并且CAR-NK细胞疗法可能是一种更广泛应用于癌症免疫治疗的方法,因为NK细胞不依赖组织相容性。TCR-T细胞能够在亚细胞区室中检测广泛的靶向抗原,在癌症治疗中具有巨大的应用潜力。已经开展了大量研究来评估基于CAR和TCR的过继性细胞疗法(ACT)的疗效和可行性。全面了解基因修饰的T细胞技术有助于这些基于过继性细胞的免疫疗法的临床转化。在此,我们系统地综述了基因修饰T细胞疗法的最新知识,并总结了CAR和TCR转基因ACT的临床前和临床试验情况。