Belrestotug

FcγR-Engaging Anti-TIGIT Antibody

TIGIT and its role in tumor immune evasion mechanisms

TIGIT is expressed on T cells, NK cells and Tregs.1-4 It competitively inhibits CD226 from binding to CD155 and CD112, thereby inhibiting T cell proliferation and inducing immunosuppressive cytokine production.2 It plays a role in tumor evasion mechanisms through the inhibition of cytotoxic T cells and promotes the Treg immune suppression function.1,2

CD, cluster of differentiation; FcγR, Fc receptor gamma chain; ITIM, immunoreceptor tyrosine-based inhibitory motif; NK, natural killer; TIGIT, T cell immunoreceptor with immunoglobulin and ITIM domain; Treg, regulatory T cell.

Belrestotug and its mechanism of action

Belrestotug is a fully human, Fc-enabled, IgG1 mAb, designed to inhibit the immunosuppressive activity of TIGIT through multiple mechanisms of action.2,5,6

Adapted from Nguyen TL-A, et al. Abstract presented at: AACR; Apr 27-28 and Jun 22-24 2020; Philadelphia.

Potent TIGIT Blockade

Belrestotug is designed to block TIGIT, to allow CD226 to interact with CD155 and CD112, leading to augmented T cell and NK cell-mediated anti-tumor immune responses2,5

Targeted Treg Depletion

Belrestotug engages with FcγR expressed on NK cells and macrophages. Engaging FcγR triggers a pro-inflammatory signal and depletes immunosuppressive Treg and TIGIT+ T cell populations through antibody-dependent cellular cytotoxicity

Cell-based assays demonstrated higher potency of belrestotug relative to other Fc-functional and Fc-silent anti-TIGIT mAbs2

Treatment of patients with belrestotug demonstrated depletion of Treg and TIGIT+ T cell populations and induced an increase in peripheral CD8+ memory T cell proliferation6

Adapted from Cuende J, et al. Poster presented at: AACR; Apr 8-13, 2022; Philadelphia.

Click to access belrestotug publications

Ab, antibody; CD, cluster of differentiation; Fc, fragment crystallizable; FcγR, Fc receptor gamma chain; IgG1, immunoglobulin G1; ITIM, immunoreceptor tyrosine-based inhibitory motif; IL-2, interleukin 2; mAb, monoclonal Ab; NK, natural killer; TIGIT, T cell immunoreceptor with Ig and ITIM domain; Treg, regulatory T cell.

Belrestotug, through its multimodal immune modulatory mechanism, has demonstrated binding to the epitope with high affinity and potency2,5,6 and depletion of Treg and exhausted T cells.6

  1. Kurtulus S, et al. J Clin Invest. 2015;125:4053–4062.
  2. Preillon J, et al. Mol Cancer Ther. 2021;20:121–131.
  3. Molfetta R, et al. Int J Mol Sci. 2020;21:922.
  4. Sanchez-Correa B, et al. Cancers (Basel). 2019;11:877.
  1. Nguyen TL-A, et al. Abstract presented at: AACR Annual Meeting; April 27-28 and June 22-24, 2020; online.
  2. Cuende J, et al. Poster presented at : AACR Annual Meeting; April 8-13, 2022; New Orleans, LA.