Bioresponsive Protein Complex of aPD1 aCD47 Antibodies for Enhanced Immunotherapy
Qian Chen,*,?,?,§,∥ Guojun Chen,?,§ Jiawen Chen,? Jingjing Shen,? Xudong Zhang,?,§ Jinqiang Wang,∥Amanda Chan,?,§ and Zhen Gu*,?,§,∥,⊥,#
?Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, 199 Ren’ai Road, Suzhou 215123, Jiangsu P.R. China
?Department of Bioengineering and§ California NanoSystems Institute, University of California, Los Angeles, California 90095, United States
∥Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695, United States
⊥ Jonsson Comprehensive Cancer Center and# Center for Minimally Invasive Therapeutics, University of California, Los Angeles, California 90095, United States
Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- “don’t eat me” signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.