Universal Prophylactic Antitumor Vaccination Using Stem Cell Membrane‐Coated Nanoparticles
Nishta Krishnan, Jiarong Zhou, Animesh Mohapatra, Christian J. Ventura, Yaou Duan, Jun-Yong Lee, Jacob J. Hoenig, Oliver Nizet, Weiwei Gao, Ronnie H. Fang, Liangfang Zhang
Abstract
Cancer vaccines are a promising immunotherapeutic modality that function by training the immune system to recognize and destroy malignant cells. As tumor-specific and tumor-associated antigens generally cannot be identified until after a tumor has already been established, these vaccines must be applied therapeutically when strong immunosuppressive mechanisms are already in place. Building upon previous work using cell membrane coating nanotechnology, the development of a broad-spectrum prophylactic cancer nanovaccine that consists of induced pluripotent stem cell (iPSC) membrane coated around an adjuvant-loaded nanoparticle core is shown. The resulting nanostructure is capable of presenting iPSC-derived oncofetal antigens, which are oftentimes re-expressed on cancer cells but lowly present on normal adult tissues. When administered in vivo, the iPSC membrane-coated nanoparticles are highly immunostimulatory and elicit strong antitumor immunity that can successfully inhibit the growth of multiple tumor types, including five different murine tumor models and in a bilaterial heterogeneous tumor model. Overall, this work demonstrates an effective approach for engineering iPSC-based nanovaccines that can be applied broadly to prevent cancer before it occurs.