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Targeting TIGIT: A novel immune checkpoint

Human monoclonal lgG1 antibody

TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains) is a novel negative immune checkpoint, expressed on T cells and NK cells.1,2

TIGIT receptor on t cells and nk cells

TIGIT is a coinhibitory receptor that binds to PVR on APCs and tumor cells in various solid and hematologic tumors.1-3 TIGIT dampens the immune response by competing with its costimulatory counterpart, CD226, for binding to PVR.1,2 Preventing PVR-TIGIT interaction may restore anti-tumor immunity, thereby complementing PD-L1 inhibition, as shown in preclinical models.1 TIGIT was identified at Genentech.2,4

Targeting PVR-TIGIT interaction may be one approach3

Tiragolumab prevents PVR-TIGIT interaction

Preclinical studies suggest that targeting both TIGIT and PD-L1 may synergistically enhance immune-mediated tumor rejection.1,5,6

Targeting TIGIT on T Cell

Targeting TIGIT may enhance Teff  function.1

Targeting TIGIT on NK Cell

Targeting TIGIT may activate NK cells.5

Targeting TIGIT on T-reg Cell

Targeting TIGIT may counter T reg-mediated immune suppression.6

APC=antigen-presenting cell; IgG1=immunoglobulin G1; NK=natural killer; PD-1=programmed cell death protein 1; PD-L1=programmed cell-death ligand 1; PVR=poliovirus receptor; Teff=effector T cell; Treg=regulatory T cell; TIGIT=T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains.

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