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Dr. Mitchell Ho
, senior Investigator at NIH and the chairman of CAS advisory board, presented a talk on
Inhibitory Antibodies Targeting Cancer Cell Signaling
. Dr. Ho’s lab is focusing on identifying novel therapeutic targets, mechanisms of inhibiting cancer signaling pathways, and technologies to target poorly immunogenic antigens or buried epitopes. He gave an overview of three antibodies (HN3, HS20, and YP7) developed in his lab that bind to different epitopes on glypican 3 (GPC3). HN3 and HS20 antibodies are capable of inhibiting the Wnt/Yap signaling in hepatocellular carcinoma cells, leading to reduced proliferation of the tumor cells. In addition, he described the work on LH7, a single domain antibody identified from a phage display library with specificity to GPC2. GPC2-directed CAR-T cells constructed based on the LH7 antibody fragment have demonstrated potent anti-tumor efficacy in mouse models. Dr. Ho also presented an update of the immunotoxins developed in the NIH immunotoxin program. Immunotoxin is an scFv-toxin fusion protein that induces protein synthesis inhibition upon internalizing into the cells. Several immunotoxins targeting CD22, CD19 and mesothelin are now in the clinical trials. In the recent years, Dr. Ho developed an anti-GPC3 immunotoxin HN3-PE38, which functions by dual mechanisms of inactivating Wnt/Yap signaling via the HN3 antibody and inhibiting protein synthesis via the PE38 toxin.
The talk from
Dr. Weichang Zhou
, CTO and SVP in the Biologics Development and Manufacturing of Wuxi Biologics, focused on
Establishing Integrated Platforms for Expediting Global Biologics Development from Concept to Commercialization
. Dr. Weichang Zhou introduced the open-access integrated platform implemented by Wuxi Biologics to facilitate process development from concept to commercialization. This platform contributed to the transformation of Callidus Biopharma from a startup company of only three employees to an important part of Amicus focusing on
next-generation Pompe ERT and complementary enzyme targeting technologies.
Dr. Janice Reichert
, Executive Director of the Antibody Society and Editor-in-Chief for mAbs journal, discussed the
Antibody Therapeutics Development Metrics
. She presented statistics on several important aspects of antibody therapeutics development, including the rates of clinical phase transition and approval, as well as lengths of the clinical development and review periods. She also analysed the variations of these statistics by therapeutic category, antibody format, origin of the antibodies, and regulatory agency designation.
The last speaker of the morning session was
Prof. Zhiqiang An
from University of Texas Health Science Center and an advisor of CAS., with a talk titled
Academic Drug Discovery: Challenges and Opportunities
. According to Prof. An, the major challenges of academic antibody drug discovery include the lack of novel antibody drug targets and biomarkers, development of drug resistance to therapeutic antibodies, and the need for technological breakthroughs such as novel methods to target intracellular proteins and deliver drugs across the blood-brain barrier. Other issues such as reproducibility of publications and decrease in government funding have further complicated the matter. Comparing the strength of academic research and industry development, he suggested that success in antibody drug discovery can be improved by an early collaboration of the academia and industry. Prof. An presented an overview of his research at Texas Therapeutics Institute, which involves identification of new immune checkpoint targets and tumor angiogenesis factors, and discovery of novel targets for breast cancer bone metastasis and brain injuries. He also underscored the importance of optimizing the dose of chemotherapies when they are used in combination with immunotherapies.
