使用体外测定对靶向淋巴细胞和髓系细胞的免疫肿瘤学候选药物进行功能评估

The growing understanding of the complexity of anti-tumor immunity provides novel targets for the development of cancer immunotherapies. However, lead selection methods can be costly and time-consuming and often rely on animal models associated with ethical considerations and limitations. In addition, new drug designs and modes of action can require the development of new or customized assays for functional screenings. In this context, IQVIA Laboratories developed a variety of in vitro assays relying on primary immune cells to enable accelerated cost-effective functional characterization of candidate drugs and lead selection. Leveraging optimized PBMC isolation and cryopreservation protocols, a large biobank of quality-controlled and well-characterized samples was generated, providing a critical component for the reliable and reproducible functional screening of drug candidates. Another critical element consists of well-established functional in vitro assays involving cultures of specific lymphoid (e.g. T cells, NK cells) and myeloid cell populations (e.g. Macrophages, Neutrophils) or complex co-cultures (e.g. cancer cells, stem cells). These assays can be used to assess immunogenicity (e.g. Neoepitopes), antigen presentation (e.g. Immunopeptidomics), macrophage phenotypes/function (e.g. M2-Suppression Assay), T cell activation (e.g. Suppressive MLR Assay, Priming Assay), Fc-functions (ADCC, ADCP and CDC), Neutrophil function (e.g. NET Formation, Trogocytosis). Several assays can also be performed with primary immune cells of animal origin (e.g. cyno, mouse, dog) with the aim of reducing animal requirement for in vivo studies. The combination of well-characterized high-quality PBMCs and a diverse panel of robust functional in vitro assays provides a useful tool for cost-effective accelerated lead selection of immuno-oncology drug candidates.