Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA.
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA; Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA; Department of Biomedical Engineering, Michigan State University, East Lansing, MI 48824, USA.
Semin Immunol. 2020 Feb;47:101390. doi: 10.1016/j.smim.2020.101390. Epub 2020 Jan 22.
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.
肿瘤相关碳水化合物抗原 (TACA) 是一类有吸引力的抗癌免疫治疗抗原。除了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 (BsAb) 是利用免疫系统对抗癌症的令人兴奋的方向。在这篇综述中，我们重点介绍了两种 TACA，即 GD2 神经节苷脂和黏蛋白 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，以及增强实体瘤穿透和减少 T 细胞耗竭和死亡的策略。此外，还介绍了减少“靶内、脱靶”副作用的方法。随着进一步的发展，针对 GD2 和 MUC1 的 CAR T 细胞和 BsAb 可以成为有效治疗实体瘤的有效药物。
