Date: 16 May 2024 (Thursday)
Time: 5:00 pm – 6:00 pm
Venue: Cheung Kung Hai Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road  

5:00 p.m.

Presenter: Xiaotian ZHANG (PhD candidate)
Primary Supervisor: Prof. Julian Alexander TANNER
Presentation Title: Targeting β-catenin degradation in cancers by aptamer-PROTAC design
Abstract: Proteolysis targeting chimera (PROTACs) are molecules consisting of two active parts linked together. One part binds to an E3 ligase, while the other part binds to a target protein. This design brings the E3 ligase close to the protein of interest, allowing for targeted protein degradation to combat disease-causing proteins. Our goal is to incorporate aptamers, which are single-stranded oligonucleotides capable of binding to a range of targets, into PROTACs. By designing a DNA aptamer-based PROTAC, we aim to target the degradation of β-catenin in different types of cancers. These cancers are characterized by mutations that prevent the degradation of β-catenin, leading to the over-activation of the Wnt signaling pathway and facilitating cancer cell proliferation and differentiation. Since β-catenin is difficult to target with small molecules, we plan to utilize the aptamer strategy instead. Aptamers, similar to antibodies but more stable and easier to produce, can fold into 3D structures and bind to various targets, including small molecules, proteins, and cells. By combining aptamers and PROTACs, we aim to specifically target the degradation of beta-catenin in various cancer types.

5:30 p.m.

Presenter: Sanxing GAO (PhD candidate)
Primary Supervisor: Prof. Rio SUGIMURA
Presentation Title: Cord blood-derived CAR macrophages engineered to express immune-priming cytokines shape immunogenic niche
Abstract: Chimeric antigen receptor (CAR) macrophage is a promising therapy for solid tumors with its capacity superior to CAR-T for infiltration into solid tumors. However, off-the-shelf generation of CAR macrophages is challenging. Here we leveraged the robustness of cord blood hematopoietic stem cells (CB-HSC) as an ideal source of CAR-macrophages. We validated the large-scale expansion of macrophages, in vitro sustainability over two weeks, and robust phagocytosis of macrophages from HSCs. We found that DNA-PK inhibition enhanced AAV-mediated knock-in at AAVS1 loci in CB-HSCs. We hypothesized that immune-priming cytokines could shape immunogenic niches for CAR macrophages. We identified that IL-12 and IL-18 primed NK cells secreting IFNγ, which are good candidates to reinvigorate the bystander cells. We will investigate the tumor-killing in the tumor-bearing NSG model. Overall, this study offers CB-HSC as an off-the-shelf source of CAR macrophages and tumor microenvironment remodeling.

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Jerry Siu at 3917 6912.