ImCheck Publishes Seminal Paper in Cell Reports Elucidating How Butyrophilins Activate Vγ9Vδ2 T cell Function Against Tumor Cells

|   Science & Medicine

  • First published study showing the role and sequential interaction of butyrophilin subtypes in the induction of cytotoxic response from human γ9δ2 T cells
  • The results support the potential of therapeutic antibodies binding to butyrophilins as an effective mechanism to engage a directed immune response against tumor cells
  • Study illustrates ImCheck’s scientific leadership in γδ T cells modulation via the butyrophilin superfamily of immunomodulators

ImCheck Therapeutics today announced the publication of preclinical data elucidating the fundamental role of butyrophilins (BTNs) in the activation of V gamma 9 V delta 2 (γ9δ2) T cells leading to an anti-tumor immune response in the peer-reviewed journal, Cell Reports. The publication, titled “BTN2A1, An Immune-checkpoint Targeting Vγ9Vδ2 T Cell Cytotoxicity Against Malignant Cells” summarizes the findings of the interaction between specific BTN subtypes that efficiently activate Vγ9Vδ2 T cells, an important subset of cytotoxic γδ T cells. In addition, the publication demonstrates that an anti-BTN2A1-specific antibody is able to inhibit the cytotoxic function of the Vγ9Vδ2 T cells. The article was authored by ImCheck scientists in collaboration with the laboratory of Prof. Daniel Olive, Professor of Immunology and Director of the Oncology Research Programs at Aix Marseille University and the company’s scientific founder.

“ImCheck was founded to advance fundamental discoveries on the role of the butyrophilin superfamily of immunomodulators in gd T cell modulation, and bring a new class of antibody-based therapeutics to patients. Today’s publication provides convincing evidence that the interaction of butyrophilins plays a major role in the activation of these crucial cytotoxic T cells,”stated Loui Madakamutil, PhD, Chief Scientific Officer of ImCheck.“As our lead program ICT01, which targets BTN3A to selectively activate Vγ9Vδ2 T cells, continues to successfully advance in its clinical development and has now demonstrated biological activity to activate Vg9Vd2 T cells in tumor patients, we value the recognition from an important journal like Cell Reports of the ground-breaking science that supports our mission of developing new therapies to treat cancer.”

Gamma-delta (γδ) T cells are an important component of the immune system and exhibit diverse functional attributes including the killing of cellular pathogens or abnormal or cancerous cells. BTNs represent a new super-family of immunoregulators present on the surface of several cell types, including cancer cells. The preclinical results published today provide key evidence that one specific BTN, BTN2A1, forms a complex with all the three isoforms of BTN3A (BTN3A1, BTN3A2, BTN3A3) to trigger the activation of Vγ9Vδ2 T cells.  These findings advance the understanding of how BTNs activate Vγ9Vδ2 T cell function against tumor cells.  In addition, the results validate ImCheck’s leadership in BTNs and the company’s development of a novel and disruptive pipeline of antibodies that target BTNs as potential therapies in oncology, autoimmune and infectious diseases.