Feb 24, 2023
RPG Seminar (2023-02-24)
Date: 24 February 2023 (Friday)
Time: 5:00 p.m. - 6:00 p.m.
Venue: Cheung Kung Hai Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road
Presenter: Miss Ka Hei LAM, PhD candidate
Primary Supervisor: Prof. Stephanie MA
Presentation Title: In vitro co-culture screen for kinase inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity
Abstract: Although immunotherapy has achieved durable clinical responses in multiple malignancies, the overall response rate to immune checkpoint blockade (ICB) for hepatocellular carcinoma (HCC) patients remains low. Accumulating evidence have shown that protein kinases play a critical role in immune evasion and tumor-immune microenvironment modulation, and thus combination therapies with protein kinase inhibitor with immune checkpoint blockade may exhibit great potential to improve clinical outcomes for HCC patients. To identify novel and targetable mechanisms of resistance to immunotherapy, we conducted a high-throughput screen based on the functional interaction of mouse HCC tumor cells and tumor-specific cytotoxic T cells for the identification of kinase inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity. A number of actionable targets have now been identified and are currently being investigated in the lab.
Presenter: Miss Ka Ching CHAN, PhD candidate
Primary Supervisor: Dr. Alan WONG
Presentation Title: Identifying gene vulnerabilities among patient-derived gastric cancer organoids by CRISPR-Cas9 screening
Abstract: Gastric cancer is the fourth leading cause of global cancer-related deaths and is particularly prevalent in East Asia. This heterogeneous disease features different histological and molecular subtypes that contribute to the differential therapeutic responses among patients. To facilitate a better characterization of therapeutic strategy among patients carrying different subtype-specific alterations, a panel of patient-derived organoids were screened with the CRISPR-Cas9 system. A library containing 2,000 sgRNAs targeting 500 kinase and phosphatase genes was created and delivered into the organoids. Genes that showed depleted sgRNA abundance were identified as potential hits that are essential for gastric cancer cell proliferation. Subsequent validation with the gene knockouts and corresponding drug treatments targeting these screened hits could help identify common and differential vulnerabilities in multiple organoids lines of different subtypes, and hence could shed light on the efficacious therapeutic regimens for patients carrying different genomic alterations.
ALL ARE WELCOME
Should you have any enquiries, please feel free to contact Miss Cynthia Cheung at 3917 9748.