Director of Science, Rhiannon Jenkinson, discusses how the use of tumor killing assays can aid oncology drug development.
Rhiannon Jenkins (00:07): The aim of many immune oncology therapies, is either to reinvigorate the immune response, or to initiate a novel, unique immune response against the tumor, which ultimately leads to tumor cell killing. Rhiannon Jenkins (00:21): When we're thinking about which cell populations are responsible for tumor cell killing, these are mostly T cell populations, so CD8 cytotoxic T cells, and natural killer or NK cells. Rhiannon Jenkins (00:33): To assess tumor cell killing, we use an NK cell-based platform, and we measure two different parameters. So we're co-culturing a tumor cell line, with PBMCs isolated from healthy human donors. Rhiannon Jenkins (00:47): And then we can read out tumor cell numbers, and the percentage of apoptotic tumor cells within these cultures. So this gives us information on whether the immune cells within that PBMC subset, are driving tumor killing over time. Rhiannon Jenkins (01:03): One of the different flavors of assays that we run, is one where we assess ADCC. So in that particular assay, we add an antibody into the tumor cell and PBMC co-culture. Rhiannon Jenkins (01:17): The antibody coats the tumor cells in a specific manner, and then that allows us to assess the amount of ADCC going on within those co-cultures. Rhiannon Jenkins (01:29): We run the tumor killing essays in two different flavors, either in a 2D format, where the PBMCs are added on top of tumor cells, which culture on a plastic, or we can run it in a spheroid format, where the tumor cells form an organoid or a ball of cells. Rhiannon Jenkins (01:47): And then we can monitor tumor cell killing in that context as well. And that particular assay setup is useful when we're thinking about antibody-dependent cellular cytotoxicity, or ADCC. Rhiannon Jenkins (02:00): And that's a very useful setting for understanding that process, and whether your therapeutic is enhancing killing in that context. Rhiannon Jenkins (02:08): We can define the subsets that are responsible within the PBMC mix for killing the tumor cells, using two different strategies. Rhiannon Jenkins (02:16): We can either deplete those subsets from the total PBMC mix, or we can take the approach where we purify the different subsets out, and add them on top of the tumor cells, and monitor tumor cell killing. Rhiannon Jenkins (02:28): On which assay set up you choose, it's very much dictated by what your therapeutic is, and your anticipated mode of action. Rhiannon Jenkins (02:37): These assays give you critical information on the mode of action of your drug, whether you're hitting your target for the expected outcomes, so are you enhancing tumor cell killing using relevant cell biology systems, before you move into efficacy models?