Materials to control immune responses can enhance anti-cancer responses within solid tumors, where the efficacy of many immunotherapies remains low. Our research focuses on the synthesis of protein-polymer conjugates and biomolecular interactions for the controlled delivery of antibodies to improve cancer immunotherapies against solid tumors with a focus on glioblastoma.<br/><br/>Antibodies for immunotherapies have shown great promise in the treatment of several brain tumors but do not readily penetrate the blood brain barrier (BBB), resulting in low efficacy after intravenous injections. Furthermore, the immunosuppressive tumor microenvironment further hinders anti-cancer T cell activities. To improve efficacy, we are developing injectable hydrogels for the Local Infusion of Immuno-Therapeutics (LIIT) such as Bispecific T cell Engagers (BiTEs), cytokines and checkpoint inhibitors to improve T cell effector function. Competitive affinity or displacement affinity release systems are incorporated into low fouling hydrogels, poly(carboxybetaine) to achieve immunotherapeutic release for several days to weeks. Sustained release will yield an antibody steady-state concentration (C<sub>ss</sub>) above the minimum effective concentration (MEC) but below the maximum tolerable concentration (MTC) for extended periods of time. To identify appropriate treatment strategies and combination therapies, we have developed a 3D embedded spheroid model to track glioblastoma spheroid growth and killing. Infusion experiments in a xenograft glioblastoma mouse model are now being conducted to determine efficacious infusion rates and durations for BiTEs as well as combination therapies.

Biomaterials for immune modulation: Local infusion of antibody immunotherapeutics

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.