Gel-based drug delivery for safe and effective cancer immunotherapy

Abstract

Immunotherapy with for instance antibodies and vaccines is a promising treatment strategy to treat cancer. A pitfall is, however, that it can induce side effects, which is often ascribed to systemic drug spread. Gels can slow down drug release and potentially limit drug spread, hence they have found increasing applications in cancer research. The goal of this thesis was to investigate how two types of gels could reduce the spread of checkpoint blocking antibodies, specifically anti-CTLA-4 antibodies. In the first part, a poloxamer based injectable gel was prepared for the controlled release of anti-CTLA-4 antibodies. Studies showed that the gel was easily injectable, reduced antibody spread, and did not induce side effects. Furthermore, antibody gel treatment resulted in effective tumor growth inhibition. The effect was enhanced when the antibody therapy was combined with photodynamic therapy. In the second part, implantable bacterial cellulose gels were prepared, which where loaded with anti-CTLA-4 antibodies. In mice, the gels strongly reduced the spread of antibodies and did not induce side effects. However, no effects on tumor growth inhibition were observed. Altogether, the results in these studies demonstrate that gels represent promising tools for safe and effective cancer immunotherapy.