Our approach

Research focused on butyrophilins and γδ T cells

Imcheck Therapeutics Science

Research focus

Rooted in the pioneering research of its scientific founder, Prof. Daniel Olive, ImCheck Therapeutics is developing a pipeline of protein therapeutic candidates targeting butyrophilins, a new superfamily of immunomodulator molecules. Its first clinical trial will be to evaluate its lead program ICT01, which targets BTN3A to activate γ9δ2 T cells, a subpopulation of unexploited killer lymphocytes.

With these novel approaches that target both the innate and adaptive immunity, ImCheck Therapeutics aims to extend the benefits of effective immunotherapy to more patients, more cancers and more diseases.

 

Butyrophilins

Immune modulation beyond the B7/CD28 superfamily

At the turn of the 21st century, work in Daniel Olive’s laboratory largely contributed to the discovery and understanding of the butyrophilins. Today, ImCheck Therapeutics is developing a series of programs to target different members of this family, of which the most advanced target is BTN3A, the main activator of γ9δ2 T cells. Importantly, BTN3A is overexpressed in various solid and hematological cancers and is often associated with a good prognosis.

Two programs targeting BTN3A are currently in development at ImCheck: an activating antibody for the treatment of cancers (program ICT01), and an antagonist antibody for the treatment of auto-immune diseases (program ICT21). ImCheck’s early-staged preclinical pipeline includes therapeutic antibodies targeting other members of the BTN/BTNL family (ICT03-ICT08) and have been designed to inhibit or activate different immune subsets (among them γ9δ2 T cells) that play a vital role in both immune-oncology (IO) and autoimmune disease (AID). All ImCheck’s programs have the therapeutic goal to strengthen the immune system to battle cancer as well as to interfere in different autoimmune diseases.


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

Harnessing the adaptive & the innate immune responses

γ9δ2 T cells are a subset of unconventional T lymphocytes that have a distinctive T-cell receptor and can recognize danger signals at the surface of stressed cells (for example, infected or cancerous cells) independently of MHC presentation. Importantly, the absence of MHC restriction implies that γ9δ2 T cells act regardless of the differences in the MHC alleles expressed by different individuals and guarantees their ability to counteract cancer cells that have lost MHC expression, a common mechanism to escape immune system detection in advanced tumors.

γ9δ2 T cells invade the tumor microenvironment, which has been associated with a favorable clinical outcome in a number of cancers (A. Gentles et al., Tosolini et al.)

γ9δ2 T cells target cancer cells directly through their cytotoxic activity and indirectly through the activation of other immune cells, which make them ideal candidates for the development of new cancer immunotherapies.


Illustration from Gamma-delta (γδ) T cells: friend or foe in cancer development? Zhao et al, J Transl Med 2018

Our Translational Research

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.