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OSE Immunotherapeutics Presents Additional Preclinical Updates on CLEC-1, a Novel Myeloid Immune Checkpoint in Immuno-Oncology

At the 2023 American Association for Cancer Research (AACR) Annual Meeting 

NANTES, France–(BUSINESS WIRE)–Regulatory News:

OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) presented two additional posters reporting the latest research updates on CLEC-1 (new myeloid immune checkpoint), from its Myeloid platform, at the 2023 American Association for Cancer Research (AACR) Annual Meeting held in Orlando (Florida) on April 14-19.

CLEC-1, novel myeloid immune checkpoint target

The academic collaboration conducted with Dr Elise Chiffoleau’s team at the Center for Translational Research in Transplantation and Immunology (1) 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.

Dr Aurore Morello, Head of Research of OSE Immunotherapeutics, comments: “Altogether, the data presented at the AACR meeting demonstrate that CLEC-1 acts as a new immune checkpoint in myeloid cells and highlight the CLEC-1/new ligand TRIM21 axis as a new target for cancer immunotherapy. These latest data generated from our teams’ collaboration provide evidence to further support the preclinical evaluation of monoclonal antagonist antibodies targeting CLEC-1. Importantly, this opens the way for further upcoming translational clinical studies aiming at developing a new myeloid immune checkpoint therapy releasing the breaks on macrophages and dendritic cells.”

“CLEC-1 inhibitory myeloid checkpoint blockade enhances antitumor responses and tumor phagocytosis by macrophages”.

CLEC-1 blockade with proprietary monoclonal antibodies increases tumor rejection in monotherapy and synergizes with chemotherapy. Anti-CLEC-1 monoclonal antibodies profoundly impacted the tumor environment: frequencies of invigorated dendritic cells and macrophages, activated cells and memory T-cells were increased, while frequencies of immunosuppressive myeloid cells and PD1-expressing T-cells were largely decreased.

The findings presented also revealed a previously unrecognized function for CLEC-1 in myeloid cells as a specific sensor of non-homeostatic cell death. The data showed that the absence of CLEC-1 suppresses tumor growth and hinders immunosuppressive tumor microenvironment.

“TRIM21 is a novel endogenous partner of the inhibitory myeloid checkpoint CLEC-1 involved in tumor antigen cross-presentation”.

TRIM21, an intra-cellular Fc receptor and E3 ubiquitin ligase, is identified as a novel interaction partner for CLEC-1 (a discovery published in Sciences Advances last November: Drouin et al., 2022). The research demonstrated the functional relevance of CLEC-1 interaction with its ligand. High TRIM21 expression is predictive of worse overall survival in patients with hepatocellular carcinoma, pancreatic cancer, or glioma. Mechanistically, CLEC-1 inhibition enhances the capacity of dendritic cells to cross-present tumor antigens to T lymphocytes, a process known to be regulated by TRIM21 through its E3 ubiquitin ligase activity. Antagonist anti-CLEC-1 or anti-TRIM21 antibodies are therefore being evaluated to further confirm the involvement of the newly identified CLEC-1 interaction with TRIM21 in the regulation of CLEC-1’s function as an inhibitory myeloid checkpoint.

(1) Collaborative academic program between OSE Immunotherapeutics and Dr Elise Chiffoleau’s research teams (Center for Research in Transplantation and Translational Immunology (CR2TI), UMR1064, INSERM, Nantes University at Nantes University Hospital, https://cr2ti.univ-nantes.fr/research/team-1).

Poster presentation details:

Poster CLEC#1

Title:CLEC-1 inhibitory myeloid checkpoint blockade enhances antitumor responses and tumor phagocytosis by macrophages””

Session Category: Immunology

Session Title: Immune Checkpoints

Session Date and Time: April 19, 2023 – 9:00 AM – 12:30 PM

Location: Section 23

Poster Board Number: 2

Poster CLEC#2

Title: “TRIM21 is a novel endogenous partner of the inhibitory myeloid checkpoint CLEC-1 involved in tumor antigen cross-presentation”

Session Category: Immunology

Session Title: Immune Checkpoints

Session Date and Time: April 19, 2023 – 9:00 AM – 12:30 PM

Location: Poster Section 23

Poster Board Number: 9

ABOUT OSE Immunotherapeutics

OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology and immuno-inflammation.

The Company’s current well-balanced first-in-class clinical pipeline includes:

OSE Immunotherapeutics expects to generate further significant value from its two proprietary drug discovery platforms, which are central to its ambitious goal to deliver next-generation first-in-class immunotherapeutics:

Additional information about OSE Immunotherapeutics assets is available on the Company’s website: www.ose-immuno.com
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Contacts

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