Dual Mechanism of EOS884448: Restoring T Cell Functions and Targeting Treg Depletion for Cancer Therapy

The abstract discusses the role of T cell Immunoreceptor with Ig and ITIM domains (TIGIT) as a co-inhibitory receptor, particularly in the context of cancer where its expression is elevated, especially in regulatory T cells (Treg). The co-stimulatory receptor CD226 competes with TIGIT for binding to PVR, suggesting a balance in cell activation. The therapeutic potential of blocking TIGIT is highlighted, as it could counteract T or NK cell dysfunction associated with cancer progression.

EOS884448, an anti-TIGIT monoclonal antibody, was identified and characterized for its strong binding to TIGIT and its ability to restore cytokine production in suppressed human primary T cells. It was produced in various formats, with the hIgG1 format showing a preference for depleting Treg cells both in vitro and in cancer patient samples. In vivo studies using surrogate mouse anti-TIGIT antibodies demonstrated that the mIgG2a isotype, which enables antibody-dependent cell-mediated cytotoxicity (ADCC), was effective in reducing tumor growth, either alone or in combination with anti-PD1 therapy. This efficacy was linked to increased activity of CD8+ and CD4+ T cells and Treg depletion within the tumor microenvironment.

The findings suggest that EOS884448 has the potential to enhance antitumor immunity through the preferential depletion of Treg cells and activation of conventional T cells, warranting further clinical investigation.

Reference: LEROY X, Hoofd C, Cuende J, et al. a-TIGIT antagonist antibody EOS884448 exhibits dual action by restoring T cell functions and selectively depleting Treg [abstract]. Presented at: American Association for Cancer Research Annual Meeting 2018; April 14-18, 2018; Chicago, IL. Cancer Res 2018;78(13 Suppl):Abstract nr LB-114.