MI2025 – Shan He

Title:
mRNA-based engineering for flexible ‘off-the-shelf’ allogeneic T cell therapy

Abstract:
Autologous T-cell therapies against cancer face disadvantages in terms of production cost, logistics, and compromised T-cell fitness. The use of allogeneic T cells can partially bypass these limitations, but it brings new challenges involving host-versus-graft (HvG) and graft-versus-host (GvH) reactions. Our aim is to develop a strategy to bypass these two obstacles by leveraging on the substantial flexibility of mRNA electroporation technology in engineering allogeneic mRNA TCR-T cells.

Instead of reducing allogeneic T cell immunogenicity through irreversible genetic approaches, we propose to prevent HvG reactions by transiently suppressing the host’s immune system with a finite treatment of immunosuppression (tacrolimus). At the same time, the functionality of these allogeneic T cells will be preserved through the conferment of transient tacrolimus resistance by introducing a modified version of calcineurin B into the T cells through mRNA electroporation. Moreover, to minimize the risk of GvH disease, we propose to utilize different cytokine cocktails to expand T cells to produce TCR-T cell products with inherently reduced GvH potential.

Biography:
Shan is now a third-year PhD student in Antonio Bertoletti’s lab. Shan was born and raised in Shaanxi province of China, where the Terra Cotta Warriors are located now. He finished his high school there and moved to Singapore to go to NTU for his undergraduate education in Biological Sciences. He worked on multiple research projects focusing on infectious pathogens during his undergrad. After he graduated, he went to Duke-NUS Medical School for his PhD, where he has been working on TCR-T cell therapy for HBV-HCC patients until today. Specifically, he works on developing an allogeneic TCR-T cell therapy product for HBV-HCC patients using the mRNA electroporation platform.