Abstract 3199: In vitro killing assays for immuno oncology candidates

The need to better understand the tumor microenvironment (TME) dictates the characterization of the cell types involved, the roles they play and how they respond to treatment. To develop better cancer immunotherapies, in vitro primary immune cell bioassays offer an early assessment of their effects on the various players of the TME. Cytotoxic cells are key players in the anti-tumor immune response. CD8+ T cells, also known as cytotoxic T lymphocytes, recognize and kill cells presenting antigens bound to MHC class I molecules, such as neoantigen present on the tumor cells. Activation of CD8+ T cells requires at least two signals from antigen presenting cells: binding of their T cell receptor (TCR) to the appropriate peptide presented on MHC I and co-stimulation by B7 binding to CD28. However, tumor environment developed different mechanisms to reduce this immune cell killing such as checkpoint inhibitors expression. In that case, the immune system will be dampened. A second type of cytotoxic cells, named Natural killer cells, are an innate immune cell type that plays an important role in anti-cancer immunity. NK cells target cells lacking MHC I expression, including cancer cells that have lost expression of MHC I. NK cells induce apoptosis in cancer cells via release of perforin and granzymes from granules, like CD8+ T cells. But here too, NK cells can be broken down by the tumor cells, notably by the PD1/PDL1 interaction. Increasing their efficacy as a therapeutic strategy has made the development of new therapeutics enhancing their anti-tumor response a priority. Those new therapeutics can have several shapes. The Antibody-dependent cell-mediated cytotoxicity (ADCC) activity of the IgG1 isotypes is one of the mechanisms that can be applied by immunoglobulin-based therapeutics. Another way to increase the killing of cancer cells is to target tumor antigens expressed by those cells using for example bispecific molecules that will enhance on the other side the T cell activation. Using primary immune cells, in vitro bioassays were developed to better screen the potential effect of new therapeutics on immune cell killing activity. Their ability to increase or induce a cytotoxic activity and facilitate the anti-tumor immune response can as a result be assessed early in the drug development process. Citation Format: Thibaut J. Janss, Juliette Lamy, Johan Arnold, Ellen Boelen, Sofie Pattijn. In vitro killing assays for immuno oncology candidates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3199.