Antibody-Conjugated Nanogel with Two Immune Checkpoint Inhibitors for Enhanced Cancer Immunotherapy.

Cancer immunotherapy by immune checkpoint inhibitors (ICIs) 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, it is shown that the development of an Antibody-conjugated NanoGel (ANGel), consisting of N-isopropylacrylamide-co-acrylic acid and antibody-binding protein (protein A), that potentiates the efficacy of two ICI mAbs (CTLA-4 and PD-L1 mAbs). Compared with mAb treatment alone, treatment with a bispecific ANGel surface-conjugated with the mAbs significantly decreases both the survival of MCF-7 and MDA-MB-231 breast cancer cells in vitro and the burden of 4T1-Luc2-derived orthotopic syngeneic tumors in vivo. The bispecific ANGel is also more potent than the conventional treatment at prolonging survival in animals with triple-negative breast cancer (TNBC). The advantage of the bispecific ANGel over other engineered bispecific antibodies arises not only from the adaptability to link multiple antibodies quickly and easily, but also from the capability to maintain the anticancer effect steadily at subcutaneously delivered tumor site. Our finding has an important implication for cancer immunotherapy, opening a new paradigm to treat solid tumors. This article is protected by copyright. All rights reserved.