Immune stealthed CAR T-cells from iPSCs for allogeneic transplantation: Engineering Next-Generation Cancer Immunotherapy
University
Anglia Ruskin University
Lead Organisation
Cambridge RNA Technologies
Theme
Health
Funding
SPARK Award
Project partners: Anglia Ruskin University & Cambridge RNA Technologies
Project focus area: Health
This project focused on developing next generation Chimeric Antigen Receptor (CAR) T-cells for the treatment of cancer and other disorders. CAR-T cells have shown strong clinical efficacy to selectively target antigen positive cells for destruction. However, the majority of current processes use the patients own, ex vivo engineered cells due to HLA mediated immune rejection of cells from healthy donors. In the course of other work, Cambridge RNA Technology has developed technology for reversible interference with HLA surface expression, required for delivery of immunogenic therapeutic cargos in its gene therapy programs. Here, we assessed the feasibility of using this same technology to permanently engineer allogeneic cells by designing and producing a single construct combining CAR along with the proprietary immune modulation cassette. This single modular construct enables simple delivery to cells. Here we differentiated and characterised T cells from induced pluripotent stem cells, in order to engineer them with the dual CAR-immune modulating cassette. We have preliminary data with engineered HEK293T cells and allogeneic lymphocytes demonstrating reduced killing correlating with HLA interference candidates. This work provides the basis for engineering the iPSC derived T-cells for CAR-T therapy and towards an engineered allogenic off the shelf CAR-T cell product.
For more information
For more information on this project, contact us, or view all Engineering Biology SPARK Award winners.
This project funding is part of the Engineering Biology Innovation Network, led by Innovate UK Business Connect in collaboration with Innovate UK and UKRI’s Technology Mission Fund. The network’s goal is to progress innovations, create a commercially focused community and foster new consortia to advance innovations towards commercial applications.