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Recent advances in tumor associated carbohydrate antigen based chimeric antigen receptor T cells and bispecific antibodies for anti-cancer immunotherapy.
Seminars in Immunology ( IF 7.8 ) Pub Date : 2020-01-22 , DOI: 10.1016/j.smim.2020.101390
Zahra Rashidijahanabad 1 , Xuefei Huang 2
Affiliation  

Tumor associated carbohydrate antigens (TACAs) are a class of attractive antigens for the development of anti-cancer immunotherapy. Besides monoclonal antibodies and vaccines, chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs) targeting TACA are exciting directions to harness the power of the immune system to fight cancer. In this review, we focus on two TACAs, i.e., the GD2 ganglioside and the mucin-1 (MUC1) protein. The latest advances in CAR T cells and bispecific antibodies targeting these two antigens are presented. The roles of co-stimulatory molecules, structures of the sequences for antigen binding, methods for CAR and antibody construction, as well as strategies to enhance solid tumor penetration and reduce T cell exhaustion and death are discussed. Furthermore, approaches to reduce “on target, off tumor” side effects are introduced. With further development, CAR T cells and BsAbs targeting GD2 and MUC1 can become powerful agents to effectively treat solid tumor.



中文翻译:

基于肿瘤相关碳水化合物抗原的嵌合抗原受体T细胞和双特异性抗体的最新进展,用于抗癌免疫治疗。

肿瘤相关的碳水化合物抗原(TACA)是一类吸引人的抗原,可用于开发抗癌免疫疗法。除单克隆抗体和疫苗外,针对TACA的嵌合抗原受体(CAR)T细胞和双特异性抗体(BsAbs)也是激发免疫系统抵抗癌症能力的激动人心的方向。在这篇评论中,我们关注两个TACA,,GD2神经节苷脂和mucin-1(MUC1)蛋白。介绍了针对这两种抗原的CAR T细胞和双特异性抗体的最新进展。讨论了共刺激分子的作用,抗原结合序列的结构,CAR和抗体构建的方法,以及增强实体瘤渗透和减少T细胞衰竭和死亡的策略。此外,还引入了减少“靶上,肿瘤外”副作用的方法。随着进一步发展,靶向GD2和MUC1的CAR T细胞和BsAb可以成为有效治疗实体瘤的强大药物。

更新日期:2020-01-22
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