OSE Immunotherapeutics has introduced the publication within the peer-reviewed journal Science Advances of information from a first-in-class preclinical program with CLEC-1, a novel myeloid immune checkpoint goal in most cancers immunotherapy.
The tutorial collaboration carried out with the workforce of Dr Elise Chiffoleau on the Nantes Transplantation and Immunology Analysis Middle (1) has made it attainable to establish CLEC-1 as a checkpoint. CLEC-1 is a receptor expressed by myeloid cells inhibiting key pro-phagocytic and cross-activating features of T cells, thereby limiting the antitumor immune response.
The article, titled “CLEC-1 is a loss of life sensor that limits antigen cross-presentation by dendritic cells and represents a goal for most cancers immunotherapy” (2), studies basic findings and preclinical outcomes exhibiting that CLEC-1 is a brand new myeloid checkpoint that interacts with a newly recognized ligand, TRIM-21, and confirming the therapeutic potential of CLEC-1 antagonist antibodies as an progressive most cancers immunotherapy.
Nicolas Poirier, CEO of OSE Immunotherapeutics, feedback: “We’re more than happy with the publication of those knowledge on CLEC-1 within the journal ‘Science Advances’. This confirms each the potential therapeutic worth of the analysis program of our progressive ‘Myeloids’ platform in immuno-oncology, and the standard of our strategic tutorial collaboration with Dr. Elise Chiffoleau’s workforce on CLEC-1. The set of outcomes on the primary ligand of CLEC-1, overexpressed by a number of kinds of tumor in people, resembling pancreatic, liver or colon cancers related to a powerful medical want, and the brand new knowledge from preclinical efficacy generated by our patented antagonist antibodies, pave the best way for future scientific improvement within the continuity of the SIRPα/CD47 axis, whose anti-SIRPα antibody is already in scientific improvement at OSE. »
Elise Chiffoleau, researcher at INSERM, explains: “We’re honored by the publication of our analysis carried out collectively with OSE Immunotherapeutics in a journal of very excessive scientific degree. Our groups labored intently on the CLEC-1 goal and recognized for the primary time TRIM-21 as an endogenous ligand induced throughout stress and/or cell loss of life. CLEC-1 is a cell loss of life receptor and binds to lifeless cells induced secondary necrosis. We found that CLEC-1 represents a brand new kind of myeloid checkpoint inside the Kind-C lectin household that controls the flexibility of type-1 dendritic cells to activate the T cell response in opposition to tumor antigens. As well as, we’ve got chosen human anti-CLEC-1 monoclonal antibodies able to prolonging survival in preclinical fashions of colon carcinoma and hepatocarcinoma. The motion of those antibodies recapitulates the adjustments within the tumor microenvironment noticed in these similar fashions by genetic deletion of CLEC-1A, with extra CD8 optimistic T cells, and in addition a change in myeloid cell composition with fewer immunosuppressive myeloid cells ( MDSCs – Myeloid Derived Suppressor Cells – and macrophages) and extra mature dendritic cells”.
The outcomes described within the scientific article present that:
– General, genetic deletion of CLEC-1 ends in profound invigoration of the tumor immune microenvironment by growing dendritic cell (antigen presenting cells) infiltrates, growing activated and reminiscence T cell infiltrates, reducing lymphocyte infiltrates T expressing the depletion marker PD1 and limiting the recruitment of immunosuppressive cells resembling MDSCs.
– Importantly, blocking CLEC-1 utilizing monoclonal antibody remedy demonstrates strong antitumor exercise, additionally by invigorating the tumor immune microenvironment in a number of preclinical oncology fashions, thus recapitulating the impact of the genetic deletion of CLEC-1 within the context of mice expressing human CLEC-1. Patented anti-CLEC-1 monoclonal antibodies enhance survival as monotherapy in an orthotopic mannequin of hepatocellular carcinoma, whereas mixture with chemotherapy will increase tumor eradication in a preclinical mannequin of colon carcinoma.
(1) Collaborative program led by the analysis groups of OSE Immunotherapeutics and Dr Elise Chiffoleau (https://cr2ti.univ-nantes.fr/analysis/team-1) of the Middle for Analysis in Transplantation and Translational Immunology (CR2TI ), UMR1064, INSERM, Nantes College, at Nantes College Hospital.
(2) “CLEC-1 is a loss of life sensor that limits antigen cross-presentation by dendritic cells and represents a goal for most cancers immunotherapy.”
Marion Drouin, Javier Saenz, Vanessa Gauttier, Bérangère Evrard, Géraldine Teppaz, Sabrina Pengam, Caroline Mary, Ariane Desselle, Virginie Thepenier, Emmanuelle Wilhelm, Emmanuel Merieau, Camille Ligeron, Isabelle Girault, Maria-Dolores Lopez, Cynthia Fourgeux, Debajyoti Sinha, Irène Baccelli, Aurélie Moreau, Cedric Louvet, Régis Josien, Jérémie Poschmann, Nicolas Poirier, Elise Chiffoleau.
Supply and visible: OSE Immunotherapeutics