|Challenge: The fight against cancer, infectious diseases and chronic disorders has been significantly advanced because of the development of effective immunotherapies, vaccines and immunomodulatory drugs. New pre-clinical tools to enable this new active field of drug discovery are needed further upstream in the discovery process. More functional and physiologically relevant readouts are necessary to address the lack of pre-clinical immunogenicity and functional data such as the phagocytosis of the targeted antigen to minimize the costly late-stage drug attrition rate.
Solution: The Immune Complex Phagocytic Assessment (ICPA) platform is based on the use of precise flow cytometry and immunological methods to evaluate and characterize targeted antigen uptake by phagocytic cells. It allows users to test and validate new vaccines as well as immunotherapies. This platform also provides the opportunity to evaluate the capacity of immunomodulatory drugs to target, uptake and destroy in vivo specific antigens by immune cells through antibody-dependent cell-mediated cytotoxicity, an important mechanism of action of immunotherapeutics.
Achievements/Impacts: Antigens from S. pneumoniae and Influenza virus were used as proof of concept for this technology. Using ICPA, the team demonstrated that specific immune sera from mice or human as well as antibody opsonization stimulate in vitro and in vivo antigen uptake and phagocytosis, leading ultimately to its degradation. In the context of cancer immunotherapy, the researchers overexpressed antigen proteins in breast cancer cells. They confirmed that the corresponding immunized sera was able to trigger phagocytosis of tumor cells by macrophages, resulting in tumor regression in a mouse model.
This platform can be implemented routinely in the R&D process. It would allow for better designs of novel immunotherapies by demonstrating target validation, immunogenicity and opsono-phagocytosis in human cell-based assays. Furthermore, this new dataset would reduce the need for unpredictive cell-based assays and the costs associated with the extensive use of animals.