OSE Immunotherapeutics SA has announced the publication of data in the peer-reviewed journal Science Advances on a first-in-class preclinical program with CLEC-1, its novel myeloid immune checkpoint target for cancer immunotherapy.
The academic collaboration conducted with Elise Chiffoleau’s team at the Center for Translational Research in Transplantation and Immunology has led to identify CLEC-1 as a checkpoint, a receptor expressed by myeloid cells inhibiting key pro-phagocytic and T-cell cross-priming functions and hence limiting anti-tumor immune responses.
The article, “CLEC-1 is a death sensor that limits antigen cross-presentation by dendritic cells and represents a target for cancer immunotherapy”, reports on fundamental discoveries and preclinical results showing that CLEC-1 is a novel myeloid checkpoint interacting with a new ligand TRIM-21 and highlighting the therapeutic potential of CLEC-1 antagonist antibodies (Abs) as innovative cancer immunotherapy.
Nicolas Poirier, chief executive officer of OSE Immunotherapeutics, commented: “We are very pleased to have this data on CLEC-1 published in the journal Science Advances. It recognizes both the significant therapeutic potential of the research program from our cutting-edge myeloid platform in immuno-oncology and the quality of our strategic academic collaboration with Elise Chiffoleau’ team on CLEC-1.
Close work on CLEC-1 target
“These findings on the first CLEC-1-ligand over-expressed in several human tumor types, such as pancreatic, liver or colon cancers with high unmet needs, alongside novel preclinical efficacy data generated with our proprietary antagonist antibodies, open the pathway for future clinical development beyond the myeloid SIRPα/CD47 axis, with anti-SIRPa antibody already in clinical development at OSE.”
Elise Chiffoleau, INSERM scientist, said: “We are honored by the publication of our collaborative research with OSE Immunotherapeutics in this journal with the highest scientific standards. Our teams worked closely on CLEC-1 target and identified for the first time TRIM-21 as an endogenous ligand induced during cell stress and/or death. CLEC-1 is a death receptor and binds to dead cells induced by secondary necrosis. We have discovered that CLEC-1 represents a novel type of myeloid checkpoint within the C-Type lectin family controlling the ability of type-1 dendritic cells to activate T-cell responses against tumor antigens.
“Furthermore, we have selected anti-human CLEC-1 monoclonal antibodies able to prolong survival in colon carcinoma and hepatocarcinoma preclinical models and recapitulating the tumor-microenvironment modifications observed in these same models by genetic ablation of CLEC-1A with more CD8+ T cells, and a shift in myeloid cell composition towards fewer immunosuppressive myeloid cells (MDSCs – myeloid derived suppressor cells – and macrophages) and more mature dendritic cells.”
The results described in the research article highlight that overall, CLEC-1 genetic deletion leads to a profound reinvigoration of the tumor immune microenvironment by enhancing infiltrates of dendritic cell (antigen presenting cells), increasing memory and activated T lymphocyte infiltrates, decreasing infiltrates of exhaustion marker PD1-expressing T lymphocytes and limiting the recruitment of immunosuppressive cells such as MDSCs.
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