PhD student – INSERM U1160, Intestinal Immunity in Inflammation and Cancer - Hôpital Saint Louis, Paris
« The 3IC team works on the intestinal immunity in inflammation and cancer, and more specifically on T cells. The intestine presents a particular immune system, constantly stimulated by exogenous antigens from food, commensal microbiota or pathogens. Specific regulations balance the immune response between tolerance of microbiota and food antigens, and protection against pathogens. This immune homeostasis is crucial and its perturbation are involved in several pathologies. Upon epithelial stress and continuous inflammation, an abnormal proinflammatory immune response can induce autoimmune reactions and chronic inflammation diseases, whereas an excessive tolerant phenotype established an immunosuppressive microenvironment favourable to cancer progression. In this tumor context, an antitumor T cell response is clearly engaged but the upregulation of immunosuppressive markers, like the immune checkpoints, allow the tumor immune escape. Immunotherapies targeting these markers, anti-PD-1 and anti-CTLA-4, were developed but presented a weak efficacy in colorectal cancer (CRC). New therapeutic strategies are necessary. In this project, we studied the antitumor T cell response involved in human CRC. Based on a prospective cohort, our objectives were to better characterize this response to find new potential target for immunotherapy and test their efficacy in our innovative autologous coculture model. We focused on several different pathways including CD39 and CD73. »
Contact IRCM : Laurent GROS
professeur d'immunologie moléculaire et directrice de l'immunologie translationnelle au Centre d'immunologie du cancer de la faculté de médecine de l'Université de Southampton
Professors Sally Ward and Raimund Ober have recently relocated their research group from the USA to Southampton. Their interdisciplinary research program is dedicated to the use of protein engineering to develop novel antibody-based therapeutics.
The identification in the Ward/Ober laboratory of the Fc receptor, FcRn, as a regulator of IgG levels and transport has resulted in significant interest in targeting FcRn in biopharma. Extensive analyses of FcRn behaviour, including subcellular trafficking studies, have led to collaborations with biopharma to develop several therapeutics that are based on modulating the interactions of IgG with FcRn. For example, one such therapeutic (Efgartigimod) that inhibits FcRn activity has been developed in collaboration with Argenx, and has recently been successfully used in phase 3 trials to treat antibody-mediated autoimmune diseases.
"The presentation will cover how a combination of antibody engineering, fluorescence microscopy and mouse disease models have been used to inform the design of therapeutics to modulate the dynamic behavior of antibodies for the treatment of autoimmunity. In particular, the targeting of the MHC Class I-related receptor, FcRn, that recycles and transports IgG to maintain IgG homeostasis will be discussed. The generation of engineered antibody-drug conjugates that are designed to deliver their cytotoxic payload more efficiently to tumor cells will also be presented"