Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing

Abstract

Inadequate Tcell activation has severely limited the success of Tcell engager (TCE) therapy, especially in solid tumors. Enhancing Tcell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated Tcell activation effects. These innovative drugs are not only armed with the powerful Tcell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity invitro and invivo. Surprisingly, they can also induce the activation of Tcell chemotaxis signals, which may promote Tcell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.