A Novel Therapeutic Against HIV Using Human T Cell Immunoglobulin Mucin (TIM-3) Ligands to Modulate Immune Response

Project by Olaf Peppard

About This Project

Researchers have showed that TIM-3 expression positively correlates with HIV-1 viral load and CD38 expression and inversely with CD4+ T cell count. Furthermore, TIM-3 is upregulated in CD8+ T cells during progressive HIV-1 infection. TIM-3 signaling suppresses effector functions of activated T-cells in HIV infections and its expression defines a distinct population of dysfunctional T cells with exceptional specificity. By blocking the interaction of TIM-3 with its ligands, these researchers were able to restore function in these T cells, resulting in increased proliferation and cytokine secretion. Thus, blocking TIM-3 could be a novel opportunity to reverse T cell anergy in HIV-1 infected patients, as well as patients with other chronic viral infections.


Project's Context

T cell exhaustion is a state of functional impairment of CD4+ and CD8+ T cells that occurs during HIV-1 infection in which T cells lose their effector functions and proliferative capacity. Addressing the underlying causes of T cell exhaustion could be a promising therapeutic avenue for patients with HIV, as well as other chronic infections. Programmed death-1 (PD-1) was one of the first identified markers of exhausted T-cells during HIV-1 infection; however, not all dysfunctional cells display PD-1 and blocking PD-1 does not fully restore T cell function.
Researchers have discovered the cell surface glycoprotein TIM-3 as a marker of exhausted T cells and that by blocking the TIM-3 pathway, they can restore T cell proliferative function and cytokine production to a greater degree than that seen with PD-1 blockage. Furthermore, TIM-3 and PD-1 are distinct populations of cells, so use of this invention in conjunction with PD-1 ligand therapy could be a powerful new treatment for HIV-1.


Project's Relevance

Blocking human T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) signaling can restore functionality to defective T cells in HIV-1 infected patients. Additionally, measuring TIM-3 provides clinicians with a novel way of evaluating, staging, and monitoring the progression of HIV infections.


Project's Goals

To develop & commercialize the technology as HIV infection therapeutic.

Institutions

Johns Hopkins University University of Oxford

Categories

Therapeutic HIV Immunology

Team

Olaf Peppard, PhD