Antibodies for immunotherapies have shown great promise in the treatment of cancer but efficacy is often limited by tumor uptake after intravenous injections. To improve efficacy, we are developing injectable hydrogels for the local sustained delivery of antibody conjugates (~100 days from a single injection) to enhance current and future immunotherapies. Sustained infusion will yield a tumor antibody steady-state concentration (C<sub>ss</sub>) above the for extended periods.  Recently, we developed a three-component drug delivery system for competitive affinity release of streptavidin-antibody conjugates from agarose-desthiobiotin hydrogels via controlled dissolution of sparingly soluble biotin derivative pellets. The streptavidin-antibody is localized in the gel through desthiobiotin complexation, and dissolution of the biotin derivative displaces desthiobiotin from the streptavidin-antibody conjugate. Streptavidin release was tuned by altering oleyl-biotin concentration to achieve first-order release for 150 days. First-order release of streptavidin-Avastin was tuned for over 100 days by varying the dissolution rate of oleyl-biotin, which was controlled the total oleyl-biotin concentration.  The bioactivity and stability of streptavidin-Avastin was confirmed by HUVEC tubulogenesis assays and LSPR binding studies. The system was determined to be non-cytotoxic through cell viability assays. For long term release applications, we require a hydrogel that does not elicit a foreign body response to prevent formation of a surrounding fibrous capsule. Therefore, we developed an injectable hydrogel composed of poly(carboxybetaine) co-polymers that crosslink through biorthogonal strain-promoted alkyne-azide cycloaddition. The hydrogels are both low-fouling and low-swelling, and suitable for long term antibody delivery.<br/>

Long term delivery of antibodies from hydrogels for local cancer immunotherapy

2019 Spring National Meeting

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