Discovery of an theranostic functional mAb for visualizing the sensitivity and effectiveness of PD-L1 checkpoint therapy

Abstract

To address the challenges of inconsistent efficacy, low sensitivity, and subjective screening methods faced by PD-L1-targeted immune checkpoint therapies in the clinic. We propose to construct a therapeutic functional monoclonal antibody with tracking capability using tetrazolium-based bioorthogonal reaction turn-on fluorescence technology, focusing on the molecular biomarker PD-L1 for easy visualisation of therapeutic response. This therapeutic monoclonal antibody enables bioorthogonal reaction turn-on fluorescence to monitoring of tumors with varying degrees of PD-L1 expression, while preserving the activity of the PDL1 monoclonal antibody and improve the immune activation rate and achieve efficient anti-tumor effects. In conclusion, our proposed family of bio-orthogonal reaction-driven fluorescence turn-on methods can be used to identify therapeutic bifunctional monoclonal antibodies to PD-L1, which can be employed alongside the screening of PD-L1 antibodies for therapeutic effects. Abbreviations: CRT, Calreticulin; DCs, Dendritic cells; ELISA, Enzyme-linked immunosorbent assay; IFN-γ, Interferon-γ; IL-2, Interleukin-2; IHC, Immunohistochemistry; WB, Western blot.

Keywords: Bioorthogonal reaction; Fluorescence turn on; In vivo screening; PDL1; Theranostic.