Redirecting cytotoxic T cells with chemically programmed antibodies. Issue 24 (15th December 2020)

• Record Type: Journal Article
• Authors: Qi, Junpeng; Rader, Christoph
• Is Part Of: Bioorganic & medicinal chemistry. Volume 28:Issue 24(2020)
• Publication Date: 2020-12-15
• Subjects: Chemical programming -- Bispecific antibodies -- Chimeric antigen receptors -- T cells -- Cancer cell surfaceome; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2020.115834
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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.