The CRUK Convergence Science Centre is a partnership between Imperial College London and The Institute of Cancer Research (ICR). We aim to bring together researchers from different disciplines across both institutions to develop innovative ways to address challenges in cancer research to benefit patients.
This seminar series brings together speakers from Imperial and ICR to present their research and how they use convergence science to answer cancer-related questions.
This session will explore strategies to enhance anti-tumour immune responses, from engineering CAR-T cells for solid tumours to modulating the immune effects of radiotherapy.
Dr Magnus Dillon (ICR)
Immune effects of radiation-induced tumour DNA damage modulation
Radiation modulates the tumour microenvironment, but its positive effects are countered by activation of immunosuppressive mechanisms. Altering DNA damage through drugs, spatial and temporal dose modulation could alter this balance. I will discuss prior work with ATR inhibitors in combination with radiation and current work looking at the immune effect of spatially-fractionated radiotherapy.
Dr Jun Ishihara (Imperial)
Making CAR-T cells efficacious but still safe for solid tumours by molecular engineering approaches
Immunosuppressive microenvironments, the lack of immune infiltration, and antigen heterogeneity pose challenges for chimaeric antigen receptor (CAR)-T cell therapies applied to solid tumours. Previously, CAR-T cells were armoured with immunostimulatory molecules, such as interleukin 12 (IL-12), to overcome this issue, but faced high toxicity. Here we show that collagen-binding domain-fused IL-12 (CBD-IL-12) secreted from CAR-T cells to target human six transmembrane epithelial antigen of prostate 1 (STEAP1) is retained within murine prostate tumours. This leads to high intratumoural interferon-γ levels, without hepatotoxicity and infiltration of T cells into non-target organs compared with unmodified IL-12. Both innate and adaptive immune compartments are activated and recognize diverse tumour antigens after CBD-IL-12-armoured CAR-T cell treatment. A combination of CBD-IL-12-armoured CAR-T cells and immune checkpoint inhibitors eradicated large tumours in an established prostate cancer mouse model. In addition, human CBD-IL-12-armoured CAR-T cells showed potent anti-tumour efficacy in a 22Rv1 xenograft while reducing circulating IL-12 levels compared with unmodified IL-12-armoured CAR-T cells. CBD fusion to potent payloads for CAR-T therapy may remove obstacles to their clinical translation towards elimination of solid tumours.
Who can attend?
Researchers, students and anyone with an interest in convergence science relating to cancer research across Imperial and ICR are welcome to register. Please email icr-imperial-convergence.centre@imperial.ac.uk to receive the registration link.