T Cell Bispecific Antibodies: An Antibody-Based Delivery System for Inducing Antitumor Immunity

Pharmaceuticals

Ryutaro Asano¹  Masahiro Yasunaga²  Daisuke Kamakura² 

[1] Department on Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan;Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan;

关键词: T cell bispecific antibody;    T-BsAb;    pharmacokinetics;    T cell redirection;    mechanism of action;    drug development;   

DOI  :  10.3390/ph14111172

来源: DOAJ

【 摘 要 】

As a breakthrough immunotherapy, T cell bispecific antibodies (T-BsAbs) are a promising antibody therapy for various kinds of cancer. In general, T-BsAbs have dual-binding specificity to a tumor-associated antigen and a CD3 subunit forming a complex with the TCR. This enables T-BsAbs to crosslink tumor cells and T cells, inducing T cell activation and subsequent tumor cell death. Unlike immune checkpoint inhibitors, which release the brake of the immune system, T-BsAbs serve as an accelerator of T cells by stimulating their immune response via CD3 engagement. Therefore, they can actively redirect host immunity toward tumors, including T cell recruitment from the periphery to the tumor site and immunological synapse formation between tumor cells and T cells. Although the low immunogenicity of solid tumors increases the challenge of cancer immunotherapy, T-BsAbs capable of immune redirection can greatly benefit patients with such tumors. To investigate the detailed relationship between T-BsAbs delivery and their T cell redirection activity, it is necessary to determine how T-BsAbs deliver antitumor immunity to the tumor site and bring about tumor cell death. This review article discusses T-BsAb properties, specifically their pharmacokinetics, redirection of anticancer immunity, and local mechanism of action within tumor tissues, and discuss further challenges to expediting T-BsAb development.

【 授权许可】

Unknown