Sanne Demandt, Group Leader for Biology at Charles River Leiden, discusses in vitro cytotoxicity testing of CAR T cells.
Sanne Demandt (00:12): Our immune system is at a very delicate balance, with under-activated cells, failing to manage pathogens, viruses, or cancer, and over-activating cells, potentially causing autoimmune diseases or cytokine release storms. Over the last decade, a major effort has been made in research to utilize our own body's T cells, and make them cancer-specific killers. Sanne Demandt (00:36): Recently, two CAR T cells have been approved by the FDA and EMA. This is a major victory for these novel therapies and the fight against cancer. The next big challenge for T cell therapies is solid tumors. Solid tumors are a challenge, because often tumor antigens are also expressed on primary human tissue. Therefore, there is a risk that these cells not only kill the cancer cells, but also damage healthy human organs. Sanne Demandt (01:01): In silico analysis of target antigen expression can provide some insight into the safety risks of these therapies. But eventually CAR T cells or TCRs will need to be tested in vitro with primary human tissues. Potential over-activation or off-target effects are part of early development and lead optimization of these therapies. Charles River has developed assays to test T cell therapies on primary human tissues, to assess cytotoxicity and activation. Through assessment of cytokine expression and percentage cell death, we were able to build a clear safety profile of novelty cell therapy against various human primary tissues.