Particle-Mediated Delivery of the Immunostimulatory Agonist Anti-CD40 for Tumor Therapy

摘要

Monoclonal antibodies against the CD40 receptor have potent immunostimulatory activity, but their clinical usage in tumor therapy has been limited by the severe systemic side effects observed in animal models and human patients. In this study, intra-tumoral injections of a nanoparticle-conjugated anti-CD40 antibody stimulate an effective anti-tumor response in mice, while minimizing adverse effects including weight loss and systemic cytokine release. The covalent conjugation of anti-CD40 to lipid-coated polymeric nanoparticles locally sequesters the agonist at the tumor, limiting its draining from the tumor into circulation and thereby minimizing systemic exposure to the agonist.