Effectiveness of slow-release systems in CD40 agonistic antibody immunotherapy of cancer

• We compare two slow-release agents, Montanide ISA 51 and dextran-based microparticles.
• CD40 agonistic antibody is delivered locally as treatment for tumors.
• Both agents reduce side-effects of high serum levels of CD40 antibody.
• Dextran microparticles cause inflammation associated with enhanced tumor-outgrowth.
• Montanide ISA 51 is the preferred slow-release agent for this treatment.

Slow-release delivery has great potential for specifically targeting immune-modulating agents into the tumor-draining area. In prior work we showed that local treatment of slowly delivered anti-CD40 antibody induced robust anti-tumor CD8+ T cell responses without systemic toxicity. We now report on the comparison of two slow-release delivery systems for their use in antibody-based immunotherapy of cancer. Anti-CD40 agonistic antibody delivered locally in mineral oil Montanide ISA 51 or in dextran-based microparticles activated tumor-specific T cell activation. Both slow-release formulations significantly decreased systemic side-effects compared to systemic administration of anti-CD40 antibody. However, dextran-based microparticles caused serious local inflammation associated with unwanted rapid outgrowth of tumors instead of the tumor clearance observed with delivery in Montanide. We therefore conclude that Montanide ISA 51 is to be preferred as a slow-release agent for CD40 agonist immunotherapy of cancer.