Research focus

Our primary focus is to develop completely novel immuno-oncology (IO) therapeutics that each target a specific BTN(L) to engage immune cells against solid tumors and hematologic malignancies. ICT01, an anti-BTN3A mAb that activates γ9δ2 T cells, a subpopulation of unexploited killer lymphocytes, has entered into clinical development in 2020. Follow-on programs targeting BTN2A and BTNL3/BTNL8 are currently in the discovery phase but demonstrate potential to modulate TAMs and δ1 T cells, respectively.

With a broad range of development programs that target both innate and adaptive immunity, ImCheck Therapeutics aims to extend the benefits of effective immunotherapy to more patients.

Butyrophilins

Immune modulation beyond the B7/CD28 superfamily

Illustration from New Insights Into the Regulation of γδ T Cells by BTN3A and Other BTN/BTNL in Tumor Immunity, Blazquez et al. Front Immunol 2018 11;9;1601

Work in Prof. Daniel Olive’s laboratory largely contributed to the discovery and understanding of the immunoregulatory properties of the BTN(L)s. Today, ImCheck Therapeutics is developing a series of programs to target different members of this family, of which the most advanced target is BTN3A, a key activator of γ9δ2 T cells. Importantly, the 3 isoforms of BTN3A are overexpressed in various solid and hematological cancers, as well as on the surface of multiple immune cell populations.

ImCheck is maximizing its drug development pipeline by generating mAbs to each member of the BTN(L) superfamily to activate or inhibit different immune cell subsets as a therapeutic approach in immuno-oncology (IO), infectious diseases, and autoimmune disease (AID), respectively.

Illustration from New Insights Into the Regulation of γδ T Cells by BTN3A and Other BTN/BTNL in Tumor Immunity, Blazquez et al. Front Immunol 2018 11;9;1601

γ9δ2 T Cells

γ9δ2 T cells are a subset of unconventional T lymphocytes that have a distinctive T-cell receptor capable of identifying stressed cells (e.g., infected or cancer cells) that express BTN3A isoforms on the surface, independently of the HLA presentation system. Being at the interface of innate and adaptive immunity, they have the appealing ability to mount effective anti-tumor or anti-infective responses: (i) direct and cytokine-mediated cytotoxicity; (ii) through their APC functions and pro-inflammatory cytokine release of IFNγ and TNFα that induce recruitment of new effector cells and activate additional members of the adaptive immune system like dendritic cells, B cells, and αβ T cells.

Exploiting the innate & adaptive immune responses against cancer

The presence of γδ T cells within tumors has been associated with a favorable prognosis in a wide range of cancers (A. Gentles et al., Tosolini et al.). Once activated, circulating γ9δ2 T cells can invade the tumor microenvironment and kill cancer cells directly through their cytotoxic activity and indirectly through the production of cytokines (IFNγ, TNFα) that recruit other immune cells (e.g., NK, T and B cells) to strengthen the anti-tumor immune response. These properties of γ9δ2 T cells make them ideal candidates to target for the next generation of cancer immunotherapies.

Exploiting γ9δ2 T cell responses against infectious diseases

As part of the first-line of defense against pathogens, circulating γ9Vδ2 T cells are capable of rapidly expanding followed by trafficking to active sites of infection to unleash their multiple anti-pathogen effector functions. Recent studies demonstrate upregulation of BTN3A expression on infected cells, which makes peripheral activation and mobilization of circulating γ9δ2 T cells with ImCheck’s BTN3A-targeted mAbs a novel, potentially pathogen-agnostic, host-directed immunotherapeutic approach.

Prof. Daniel Olive, MD, PhD.

Scientific founder of ImCheck Therapeutics
Head of the Immunity and Cancer Department - Cancer Research Center of Marseille, France.

Our Translational Research

The comprehensive bench-to-bedside research environment offered by the Marseille Cancer Research Center, the Paoli-Calmettes Cancer Institute, and Marseille Immunopole provides favorable conditions for our team to conduct discovery & clinical research in the field of immunotherapy. We will continue to actively explore and monitor patients’ immune systems with the goal to develop molecules controlling adaptive and innate immune responses that provide safe and effective alternatives to the currently available treatments.