Dr. Eli Gilboa Receives Avant-Garde Award from NIH for HIV/AIDS Research

University of Miami Miller School of Medicine researcher Eli Gilboa, Ph.D., is one of five scientists selected from across the nation to receive a 2015 Avant-Garde Award for HIV/AIDS research from the National Institute on Drug Abuse, part of the National Institutes of Health.

Gilboa, professor of microbiology and immunology and Director of the Dodson Interdisciplinary Immunotherapy Institute, was selected for his proposal to develop novel drugs to successfully restore the function of T cells, which are critical in immune response. This proposal has the potential to transform therapies for HIV/AIDS patients, including substance users whose drug use has further undermined their immune function.

“A major challenge for HIV-infected patients is that the immune system, particularly for drug abuse patients, is becoming progressively dysfunctional,” said Gilboa, also a member of the Sylvester Comprehensive Cancer Center, who has focused much of his research on developing immune-based treatments for cancer.

Gilboa explains that the immune system, especially in HIV/AIDS patients, can become “exhausted” and dysfunctional, which leads to disease progression. That has researchers making a big push to restore functionality of the T cells, a subset of immune cells particularly adept at combating HIV. Recently, scientists made a key discovery: those “exhausted” immune cells in HIV-infected patients have receptors on the surface, the main one known as PD-1, that inhibit their function, and thereby providing a potential target. The goal is to block those inhibitory receptors.

Blocking such receptors with antibodies has been used with great success in cancer. Gilboa explains that the goal in his work is to apply that same principle to HIV. The problem and challenge, he said, is “there is more than one receptor. You block one and there’s another.”

Instead, Gilboa is looking into the cell, targeting an intracellular mediator that “services” all the receptors. However, unlike receptors expressed on the cell surface, antibodies cannot be used because they fail to penetrate into the cell. Gilboa proposes using a novel drug delivery system that is made up of short nucleic acids that can be synthesized chemically and therefore relatively inexpensively.

“This platform is one of the unique and critical features of our proposal,” said Gilboa. There are two components: the therapeutic agent, a nucleic acid that blocks the function of the intracellular mediator of immune dysfunction thereby reactivating the T cell’s natural immune response, which is attached to a second form of nucleic acid, a targeting ligand that acts as a missile binding specifically to the T cells, delivering the therapeutic cargo.

“This award to Dr Gilboa is highly significant because of its potential to bring us closer to a ‘cure’ for HIV/AIDS,” said Savita Pahwa, M.D., Director of the Miami Center for AIDS Research. “Antiretroviral drugs can suppress the virus, but it hides in latent reservoirs which are invisible to the immune system and comes roaring back if the HIV drugs are stopped. A combination approach that also includes Dr. Gilboa’s strategy to arm killer T cells has the highest probability to eliminate virus-infected cells. We are very excited about his work, all the more as it bridges basic science with clinical science in the area of drug abuse – a high priority area for the Miami CFAR.”

Gilboa and each of the four other recipients will receive $500,000 annually for five years. The annual Avant-Garde Award competition, now in its eighth year, is intended to stimulate high-impact research that may lead to groundbreaking opportunities for the prevention and treatment of HIV/AIDS in drug users.

“The Avant-Garde Award provides us with the unique opportunity to develop a novel nucleic acids based drug and drug delivery platform to block key intracellular pathways that mediate immune dysfunction,” said Gilboa.

The other scientists who received a 2015 Avant-Garde Award are Don C. Des Jarlais, Ph.D.,
Mount Sinai Beth Israel in New York City; Nichole Klatt, Ph.D., University of Washington in Seattle; Alan D. Levine, Ph.D., Case Western Reserve University in Cleveland; and Tariq M. Rana, Ph.D., University of California San Diego.

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