The NIH is pitching $14.6 million into a “three for one” HIV research program led by USC and the Fred Hutchinson Cancer Research Center that aims to strike the need for daily medication — or even achieve a “home run” cure.
The five-year grant will back preclinical studies that combine gene editing with technology to improve bone marrow transplants. The potential therapy would engineer a patient’s own stem cells to fight HIV, and stimulate them to produce new immune cells once reintroduced to the patient.
“A home run would be that we completely cure people of HIV,” Paula Cannon, a USC professor of molecular microbiology and immunology and co-director of the program, said in a statement. “What I’d be fine with is the idea that somebody no longer needs to take anti-HIV drugs every day because their immune system is keeping the virus under control, so that it no longer causes health problems and, importantly, they can’t transmit it to anybody else.”
Hans-Peter Kiem, the Stephanus Family Endowed Chair for Cell and Gene Therapy at Fred Hutch, is the co-director. Harvard University professor David Scadden and Magenta Therapeutics are also collaborating on the project.
The approach was inspired by three patients who appear to have been cured of the virus — all of whom received blood stem cell transplants from donors who carried a mutation in the CCR5 gene. One of them, dubbed the “Berlin patient,” has been off antiretroviral drugs since 2007.
“I think of the Berlin patient as proof of principle that replacing the immune system with one that’s HIV-resistant by removing CCR5 is a possible way to treat somebody,” Cannon said.
The program will study the use of gene editing to remove CCR5 from patients’ stem cells — a process which is already in clinical trial for HIV treatment at City of Hope National Medical Center in Duarte, CA. The stem cells will also be engineered to release antibodies and antibody-like molecules that block HIV.
In addition, the grant will fund a Fred Hutch team’s endeavor to adapt CAR-T cell therapy to create stem cells whose progeny target HIV-infected cells.
As for preparing a patient for the transplant, Magenta is working on antibody-drug conjugates to replace mild chemotherapy or radiotherapy typically given before the procedure. And Scadden is researching an injectable gel that could help immune cells repopulate more quickly, avoiding a delay.
HIV infection, which currently affects about 1.2 million Americans, has proved to be exceedingly difficult to cure. In July, Merck and Dewpoint inked a deal that allows the pharma to use the Boston-based biotech’s biomolecular condensate technology to develop treatments, and potentially a cure, for the HIV virus. The NIH-funded group is hoping to at least control the virus enough to eliminate the need for daily meds. But at best, they’re also eyeing a long sought-after cure.
“This grant funds a team with an overarching goal of developing what our perfect HIV gene therapy would look like,” Cannon said. “All of these pieces could happen separately, but the fact that the NIH has funded us as a team means that the sum will be so much bigger than the parts.”