Timing of Immunotherapy Crucial to Outcomes

MedicalResearch.com Interview with:

Tatiana Garcia-Bates, Ph.D. Research Assistant Professor Department of Infectious Diseases and Microbiology Graduate School of Public Health University of Pittsburgh

Dr. Garcia-Bates

Tatiana Garcia-Bates, Ph.D.
Research Assistant Professor
Department of Infectious Diseases and Microbiology
Graduate School of Public Health
University of Pittsburgh

MedicalResearch.com: What is the background for this study?

Response: Human immunodeficiency virus (HIV) infection is now a manageable disease with the advent and availability of highly effective, combination antiretroviral therapy (ART). Unfortunately, as soon as ART is interrupted, the virus quickly rebounds to high levels and again targets the immune system. Therefore, new immunotherapeutic treatments are sought to re-program the immune system to control the virus after ART interruption.

In many ways, chronic HIV infection, even when controlled, resembles cancer in how it impacts the immune system. Both conditions for example are associated with immune dysfunction, where the immune cells (specifically T cells) that are supposed to protect our bodies against invading microorganisms or cancers become exhausted and fail to respond effectively. In cancer, effective immunotherapies have been developed to reverse this immune exhaustion to extend the fighting capacity of the T cells.

An example of this is drugs that target immune checkpoints, or “shut down” proteins, expressed on activated T cells, such as the programmed death-1 (PD-1) receptor. When engaged, PD-1 sends a negative signal to deactivate the T cell, and this contributes to the immune exhaustion seen in both cancer and in chronic infections. Some cancers express the ligand or the “trigger” for this shut down receptor, called PD-1 ligand (PD-L1). When this interaction between PD-1 and PD-L1 is interrupted, for example by using a blocking antibody, T cells can regain their killing capacity and destroy infected cells or cancer cells. This anti-PD-1 therapy has demonstrated high success against a variety of tumors.

Therefore, we tested this approach in the context of HIV infection using a well-characterized cohort of HIV-positive individuals to see if we could improve their T cell responses to HIV in a laboratory setting.

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