School of Biomedical Sciences & School of Biological Sciences cordially invite you to join the following seminar:

Speaker: Dr Dongfang Liu, MD, PhD, Rutgers University, USA
Talk Title: CD147-CAR-NK for solid tumor treatment and immunological synapse application

Date: 6 August 2024 (Tuesday)
Time: 10:00 am – 11:00 am
Venue: 6N-11, Kadoorie Biological Sciences Building, The University of Hong Kong
Host: Professor Rio Sugimura (School of Biomedical Sciences) and Professor Heath Johnson (School of Biological Sciences)

Biography

Dongfang Liu, Ph.D., an Associate Professor with tenure, Director of Immunoassay Development Program at the Department of Pathology, Immunology and Laboratory Medicine, Scientific Director of Cellular Imaging & Histology Core in Rutgers University- New Jersey Medical School. In 2012, Dr. Liu was recruited to Baylor College of Medicine as a tenure-track Assistant Professor in the Department of Pediatrics, and Pathology & Immunology, before joining Houston Methodist Research Institute (HMRI) as an Assistant Professor in 2015.  In 2018, Dr. Liu was promoted to an Associate Professor in HMRI. Dr. Liu did his Ph.D. and postdoctoral training on natural killer (NK) cells. After completing the postdoctoral training, he joined Ragon Institute of MGH, MIT and Harvard in 2011 as a senior research scientist, where he worked on HIV-specific immune cell dysfunction. Dr. Liu’s research is primarily focused on the immunobiology of NK, chimeric antigen receptor (CAR)-NK cells, and immune synapse biology and application. He has more than 20 years' experience in NK cell research. Dr. Liu has published research papers in top-tier journals, including Nature Immunology, Immunity, Nature Communications, JACI, Proc. Natl. Acad. Sci., and others.  Dr. Liu serves on several editorial boards for multiple journals and as a reviewer for a number of journals and several grant agencies. 

Abstract

Recent clinical trials testing cancer immunotherapies have shown promising results for the treatment of various cancers. One such therapy involves engineering immune cells to express chimeric antigen receptors (CAR), which combine tumor antigen specificity with immune cell activation in a single receptor. The adoptive transfer of these CAR-modified immune cells (especially T cells, CAR T) into patients has shown remarkable success in treating multiple refractory blood cancers. However, in order to achieve the promise of CAR-modified immune cells in treating solid tumor cancers, further advances will be required. One key challenge is identifying a safe and effective solid tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin (BSG) or extracellular matrix metalloproteinase inducer (EMMPRIN), can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells (including T and NK cells) for HCC patients. The machine-learning immunological synapse quality can be used to predict the efficacy of CD147-CAR cell therapies. The results of these studies will also streamline the path to clinical trials of logCD147-CAR-T or -NK cells for adoptive cell therapy for the treatment of HCC. This study could be translated to the treatment of other CD147 positive solid tumor cancers as well in the future. 

ALL ARE WELCOME
Should you have any enquiries, please feel free to contact Miss Crystal Chan at 3917 6830.