Characterization of Site-Specific Q295-Conjugated TLR7 Agonist Immune-Stimulating Antibody Conjugates

Author: Samuel Chung

Field of Study: Chemistry

Program Affiliation: Undergraduate Research Award (URA)

Faculty Mentors: Nathan Tumey

Easel: 89

Timeslot: Afternoon

Abstract: Recent advances in immunotherapy as a viable cancer treatment modality has led to the development of immune-stimulating antibody conjugates (ISACs), which aim to induce adaptive and innate immune responses to engage with tumors. Previously, the Tumey lab has explored “Hinge” conjugated ISACs employing an imidazole[4,5-c]quinoline Toll-Like Receptor 7 (TLR7) agonist, however these ISACs face issues of aggregation, poor pharmacokinetics, and heterogeneity. However, the new site-specific Q295-conjugation method developed by the Tumey lab was hypothesized to alleviate the aforementioned issues, as it allows for controlled addition of linker-payloads to a thiolated Q295 site of antibodies. Herein, this work aims to optimize the Q295 method for generating ISACs employing TLR7 agonists. Additionally, Q295 conjugates are characterized and evaluated against their Hinge counterparts in a variety of co-culture models for NF-κB activation and IL-6 release, as well as lysosomal payload release assays to elucidate possible differences in release kinetics affecting efficacy.