Yu-Hsun Lo

Research Fellow
Development Center of Biotechnology

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Dr. Yu-Hsuan Lo obtained his Ph.D. from the Institute of Microbiology and Immunology at National Yang-Ming University, where his doctoral research focused on the signal transduction and activation mechanisms of the T cell receptor. After completing his Ph.D., he pursued postdoctoral training at the Institute of Molecular Biology, Academia Sinica, and subsequently at the La Jolla Institute for Immunology in California, USA. During this period, his research scope expanded to include the molecular mechanisms governing NLRP3 inflammasome activation and its regulation. His findings in this area were published in the peer-reviewed journal Blood.
In 2015, Dr. Lo joined the Development Center for Biotechnology (DCB) as a research scientist in the Protein Engineering Department and was promoted to Director of the Department in 2019. During his period at DCB, Dr. Lo led the team in establishing DCB’s first fully human antibody library, which significantly enhanced the organization's capabilities in early-stage therapeutic antibody screening. Notably, this antibody library facilitated the development of a novel anti-B7-H3 monoclonal antibody, which is currently under investigation for use in antibody-drug conjugate (ADC) therapeutics.
Recognizing the growing prominence of ADCs in therapeutic antibody development, DCB has also been actively involved in advancing ADC technology platforms. Current research focuses on optimizing intracellular trafficking and payload delivery through antibody screening strategies, with the goal of enhancing the therapeutic efficacy of next-generation ADCs.

Speech title & Synopsis

LYSward: An Engineering Platform for Generation of pH-Dependent Antibody Drug Conjugate to Enhance Antitumor Activity

FDA approved 15 Antibody-Drug Conjugates (ADCs) by 2025 due to their high potency in clinical. The mechanism of action of ADCs involves the binding of the ADC to tumor-associated antigens on the surface of tumor cells, triggering endocytosis and subsequent releasing cytotoxic small-molecule drugs within lysosomes to kill the tumor cells. However, recent studies have shown that after ADCs bind to tumor antigens and are internalized, only about half of ADC-antigen complexes enter late endosomes and lysosomes. The rest of complexes are recycled back to the cell surface by way of recycling endosomes. and it
leads to reduce the intracellular drug accumulation and diminish cytotoxic effects against tumor cells. On the other hand, if ADC and antigen complexes do not dissociate and enter late endosomes and lysosomes, the whole complex are result in degradation, damages and losses of targeted antigens. This in turn decreases the efficiency of subsequent ADCs uptake by low and medium antigen expression cancer cells, thereby reducing the overall anti-tumor effect and inducing drug resistance. These observations suggest that the dissociation of the ADC-antigen complexes in the endosome is a critical step in enhancing the intracellular delivery efficiency of ADCs. Based on this concept, DCB developed the LYSward technology to screen antibodies with reduced antigen-binding affinity under the low pH environment of endosomes (pH 5.8). In vitro studies revealed that, relative to wild-type antibodies, point-mutated antibodies with pH sensitivity displayed increased internalization by tumor cells and enhanced tumor cell-killing efficacy. These findings validate the utility of DCB’s LYSward platform as a powerful tool for the development of next-generation antibody-drug conjugates (ADCs)