Peter Yingxiao Wang

Peter Yingxiao Wang
Department Chair, Dwight C. and Hildagarde E. Baum Professor, Alfred E. Mann Dept. of Biomedical Engineering
University of Southern California (USC)

Title: Remote Control of Genetics/Epigenetics and Cellular Functions for Cancer Immunotherapy

Abstract: Cell-based cancer immunotherapy is quickly emerging as a promising therapeutic intervention for cancer treatment. However, non-specific killing against healthy tissues (e.g. on-target/off-tumor effect) is a major hurdle for solid tumor treatment. Here we show that the genetics and cellular functions of chimaeric antigen receptor T cells (CAR-T cells) within tumors can be remotely controlled by focused ultrasound (FUS) via a CAR cassette under a controllable promoter. In mice with subcutaneous tumors, locally injected T cells with the inducible CAR and activated via FUS guided by magnetic resonance imaging (MRI) mitigated on-target off-tumor activity and enhanced the suppression of tumor growth, compared with the performance of standard constitutive CAR-T cells. We have also developed controllable on-switch gene cassettes to reprogram the target cancer cell by FUS. Viral vectors were used to deliver the gene cassettes into the tumor cells, which will be activated by FUS and then targeted by CAR T for cancer immunotherapy. We applied this system to successfully treat prostate cancer cells whose locally metastasized tumors are confined in space but intermingled with vessels and nerves, with surgery or radiation therapy targeting the whole prostate gland potentially having adverse urinary and sexual effects on the patients. This local activation of engineered cells by FUS should allow a high precision and safety in eradicating tumors. Recently, we have also integrated FUS and CRISPR technologies to remotely guide the focused genomic editing and regulations in vivo. Hence, this approach for immunotherapy should open new opportunities to integrate engineering physics with genetic medicine and lead to successful translation from fundamental science and engineering to cancer therapy and clinical applications.

Bio: Dr. Wang obtained his bachelor’s and master’s degrees in Mechanics and Fluid Mechanics from Peking University, Beijing, P.R. China, in 1992 and 1996, respectively. He received his Ph.D. degree in Bioengineering from the University of California, San Diego Jacobs School of Engineering in 2002 and continued his postdoctoral work at UC San Diego working under Bioengineering Professor Shu Chien and Professor Roger Y. Tsien in the Department of Pharmacology. He is current the department chair and a professor in the department of Biomedical Engineering at USC and a fellow of American Institute of Medical and Biological Engineering (AIMBE), International Academy of Medical and Biological Engineering (IAMBE), and Biomedical Engineering Society (BMES). Before joining the USC in 2023, he was a faculty of Bioengineering at the University of Illinois, Urbana-Champaign (UIUC), and University of California, San Diego (UCSD). Dr. Wang is the recipient of the Wallace H. Coulter Early Career Award (both Phase I and Phase II), the National Science Foundation CAREER Award, and National Institutes of Health Independent Scientist Award. His research is on cellular and molecular engineering for live cell imaging and controllable cell-based therapy. His lab is supported by the National Institutes of Health, National Science Foundation, and private foundations.