Antibody-conjugating nanogel (Conjugel) with two immune checkpoint inhibitors for enhanced cancer immunotherapy

Abstract

Cancer immunotherapy by immune checkpoint inhibitors (ICI) acts on antitumor responses by stimulating the immune system to attack cancer cells. However, this powerful therapy is hampered by its high treatment cost and limited efficacy. Here, we show the development of an antibody-conjugating system (Conjugel) that potentiates the efficacy of bispecific immunotherapy that simultaneously targets CTLA-4 and PD-L1. The Conjugel, consisting of highly deformable nanogels and antibody-binding protein, was loaded with two ICI monoclonal antibodies (mAb). Compared with mAb treatment alone, treatment with a bispecific Conjugel loaded with the both ICIs significantly decreased both the survival of MCF-7 and MDA-MB-231 breast cancer cells in vitro and the size of 4T1-Luc2-derived orthotopic syngeneic tumors in vivo. Furthermore, the ICI-loaded Conjugel was less toxic in vivo than the combination treatment delivered as a bolus. Our findings have important implications for Conjugel-based immunotherapy, developing the safer and higher efficacy of ICIs to treat breast cancers.