Programming T Cell Immunity with Nanomaterials

Recent innovations in tumor exome sequencing have signaled the new era of personalized immunotherapy with patient-specific mutated tumor antigens (neoantigens), but a general method for stimulating strong antitumor T cell responses against such antigens remains lacking. We demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with tumor antigen peptides and adjuvants can markedly improve the delivery of antigens and adjuvants to lymphoid organs and sustain antigen presentation on dendritic cells, resulting in potent T cell responses that are up to 47-fold stronger than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials. Multi-epitope vaccination generated broad-spectrum T cell responses against tumor-associated antigens and neoantigens. Moreover, the potent T cell responses synergized with checkpoint inhibitors to efficiently eliminate tumors and protected survivors against tumor recurrence. Our work represents a new powerful approach for cancer immunotherapy and suggests a general strategy for personalized nanomedicine.

Rui Kuai received his B.S. and M.S. from West China School of Pharmacy, Sichuan University and Ph.D. in Pharmaceutical Sciences from the University of Michigan. He is currently a postdoctoral research fellow in the laboratory of Prof. Jeffrey Karp at Harvard Medical School and the Center for Nanomedicine at Brigham and Women’s Hospital. His research has focused on using pharmaceutical approaches to modulate the immune system for the treatment of cancer and other immune-related disorders. To date, he has published 2 U.S. patents, 1 book chapter, and 26 articles in high profile journals such as Nature Materials, Science Advances, ACS Nano, and Nature Communications, with a total of > 1000 citations. He is the recipient of a number of prestigious awards including the American Heart Association (AHA) Predoctoral Fellowship, Chinese Government Award for Outstanding Self-financed Students Abroad, and American Association of Pharmaceutical Scientists (AAPS) Innovation in Biotechnology Award.