TIGIT Blockade: A Multipronged Approach to Target the HIV Reservoir

Abstract

During chronic human immunodeficiency virus type 1 (HIV-1) infection, upregulation of inhibitory molecules contributes to effector cell dysfunction and exhaustion. This, in combination with the ability of HIV-1 to reside dormant in cellular reservoirs and escape immune recognition, makes the pathway to HIV-1 cure particularly challenging. An idealized strategy to achieve HIV-1 cure proposes combined viral and immune activation by "shock"ing HIV-1 out of latency and into an immunologically visible state to be recognized and "kill"ed by immune effector cells. Here we outline the potential for blockade of the inhibitory immune checkpoint T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) to overcome natural killer (NK) cell and T cell inhibition associated with HIV-1 infection and invigorate antiviral effector cell responses against HIV-1 reactivated from the latent cellular reservoir.

Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma

“…Recently, the anti-TIGIT therapeutics have drawn great attention in treating colorectal cancer, breast cancer, and melanoma through modulating the activities of CD8 + T, T-reg, and NK cells 61 . Blockage of CD112R and TIGIT signaling sensitizes human natural killer cell cytotoxicity functions on melanoma 62 .…”

Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World

“…To further enhance durable T cell immunity, a number of approaches are being pursued to reverse the immune dysfunction induced by progressive HIV disease. Thus, immune checkpoint blockers such as pembrolizumab (anti-PD1) and ipilimumab (anti-CTLA4) are being evaluated for their ability to augment HIV-specific functional immune responses, [39][40][41] vedolizumab (anti-a4b7) for its ability to reduce trafficking of susceptible CD4 + T cells to the gut HIV reservoir, 42 and the IL-15 superagonist ALT-803/N-803 for its ability to improve trafficking of CD8 + T cells to lymphoid tissue B cell follicles. 43,44 A variety of other agents (e.g., sirolimus, an IL-21 superagonist, and anti-IFNa/b receptor antibodies) are also being tested for their ability to reduce HIV-associated inflammation, hoping to thereby improve HIV-specific immune responses.…”

Live-attenuated oral polio vaccine as a potential source of protection against COVID-19 – Review of literature

“…[ 42 , 43 ] TIGIT (T-cell immunoglobulin with immunoreceptor tyrosine-based inhibitory motif domain) is a recently discovered immune checkpoint molecule belonging to immunoglobulin superfamily with potential antiviral and anti-tumor activity due to its immune inhibitory effect on T cells and NK cells. [ 42 , 44 ] It interacts with the costimulatory receptor DNAM-1 and the inhibitory receptors TIGIT and CD96, resulting in either immune cell activation or inhibition, respectively. [ 38 , 42 ] Binding affinity of PVR/CD155 is higher for TIGIT (inhibitory molecule) compared to CD226 (costimulatory molecule).…”

“…[ 42 , 44 ] It interacts with the costimulatory receptor DNAM-1 and the inhibitory receptors TIGIT and CD96, resulting in either immune cell activation or inhibition, respectively. [ 38 , 42 ] Binding affinity of PVR/CD155 is higher for TIGIT (inhibitory molecule) compared to CD226 (costimulatory molecule). [ 38 , 42 ] Hence, CD155/PVR modulates the immune response depending on binding affinity and downstream receptor binding at the cell surface.…”

“…[ 38 , 42 ] Binding affinity of PVR/CD155 is higher for TIGIT (inhibitory molecule) compared to CD226 (costimulatory molecule). [ 38 , 42 ] Hence, CD155/PVR modulates the immune response depending on binding affinity and downstream receptor binding at the cell surface. [ 38 ]…”