Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL 33458, USA.
Bioorg Med Chem. 2020 Dec 15;28(24):115834. doi: 10.1016/j.bmc.2020.115834. Epub 2020 Nov 2.
T-cell engaging bispecific antibodies (T-biAbs) mediate potent and selective cytotoxicity by combining specificities for target and effector cells in one molecule. Chemically programmed T-biAbs (cp-T-biAbs) are precisely assembled compositions of (i) small molecules that govern cancer cell surface targeting with high affinity and specificity and (ii) antibodies that recruit and activate T cells and equip the small molecule with confined biodistribution and longer circulatory half-life. Conceptually similar to cp-T-biAbs, switchable chimeric antigen receptor T cells (sCAR-Ts) can also be put under the control of small molecules by using a chemically programmed antibody as a bispecific adaptor molecule. As such, cp-T-biAbs and cp-sCAR-Ts can endow small molecules with the power of cancer immunotherapy. We here review the concept of chemically programmed antibodies for recruiting and activating T cells as a promising strategy for broadening the utility of small molecules in cancer therapy.
T 细胞衔接双特异性抗体（T-biAbs）通过将靶细胞和效应细胞的特异性结合在一个分子中，介导强大而特异的细胞毒性。化学程序化 T 细胞衔接双特异性抗体（cp-T-biAbs）是由以下两种成分精确组装而成：（i）小分子，以高亲和力和特异性控制癌细胞表面靶向；（ii）抗体，招募和激活 T 细胞，并赋予小分子受限的生物分布和更长的循环半衰期。与 cp-T-biAbs 概念上类似的是，可切换嵌合抗原受体 T 细胞（sCAR-T）也可以通过使用化学程序化抗体作为双特异性衔接分子来受到小分子的控制。因此，cp-T-biAbs 和 cp-sCAR-Ts 可以赋予小分子癌症免疫治疗的能力。在这里，我们回顾了招募和激活 T 细胞的化学程序化抗体的概念，这是一种有前途的策略，可以拓宽小分子在癌症治疗中的应用。
