Abstract: The therapeutic efficacy of combined chemotherapy and immunotherapy in solid tumors remains limited due to insufficient tumor targeting and accelerated T cell exhaustion driven by the immunosuppressive tumor microenvironment (TME). To address these challenges, we have identified novel antibodies targeting key immunotherapy markers, and applied computer-aided design to engineer these antibodies with optimized properties. Furthermore, we developed antibody-directed therapeutic strategies capable of modulating tumor metabolism, remodeling the immune landscape, and enhancing antitumor activity. Using yeast display in combination with computational design, these antibodies can be re-engineered into high-affinity variants that mediate tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC) via natural killer (NK) cells. In addition, these antibodies can be converted into bispecific antibodies targeting both tumor cell antigens and NK cell markers, thereby recruiting NK cells to eliminate tumor cells. We also constructed chimeric antigen receptor (CAR)-modified T cells targeting non-small cell lung cancer (NSCLC). These findings support the further development of this class of therapeutic strategies in both preclinical and clinical studies.

Biography: Professor Qi Zhao is an Associate Professor at the Faculty of Health Sciences, University of Macau. He also serves as the Director of the Hengqin UM–China Resources Joint Laboratory, and as President of the Macau Bioinformatics Society and the Macau Stem Cell Research Society. In addition, he is an Associate Editor of journals including Molecular Cancer. He received his bachelor’s degree from Jilin University and earned his PhD from The Chinese University of Hong Kong. He subsequently completed postdoctoral training at the U.S. National Institutes of Health (NIH) and Memorial Sloan Kettering Cancer Center. Professor Zhao has received several honors, including the NIH Federal Technology Transfer Award and the Best Teacher Award of the Faculty of Health Sciences at the University of Macau. He has been listed for five consecutive years in the Stanford University Top 2% Scientists ranking. His research team focuses on the development of antibody targeted cancer therapies and has been supported by major grants from the Ministry of Science and Technology of China, the Macau Science and Technology Development Fund, and the NSFC–Macau Joint Fund. He has published 160 peer reviewed papers, including works in Cell Reports Medicine, Nature Communications, Clinical Cancer Research, and JACS, and holds over 20 invention patents. He has also developed multiple antibody based therapeutics, among which two first in class monoclonal antibody drugs have entered clinical trials in the United States.