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Engineered Immune, Stem Cells Studied for HIV Cure

HIV released from cell

Illustration of HIV released from the surface of an infected cell (Bette Korber, Los Alamos National Lab)

17 June 2020. Academic and industry researchers are investigating engineered immune-system cells combined with stem cells as an immunotherapy to neutralize HIV viruses and cure infections. The five-year preclinical project by a team from University of California in Los Angeles, biotechnology company CSL Behring, and Fred Hutchinson Cancer Research Center is funded by a $13.7 million grant from National Institutes of Health.

The researchers are seeking to apply recent advances in cancer immunotherapies with genetically-engineered T-cells from the immune system that add chimeric antigen receptor or CAR proteins, which enable the T-cells to act like antibodies to attack cancer cells. The team, led by AIDS researchers Scott Kitchen and Irvin Chen at UCLA, is also building on recent discoveries showing stem cells with a mutation that prevents the human immunodeficiency virus from binding to host cells. In one case, the so-called Berlin patient, received two blood forming stem-cell transplants beginning in 2007, leading to long-term remission of his HIV infections.

But as Timothy Ray Brown, the Berlin patient, notes, his case is unique because of a living stem cell donor with an almost perfect genetic match, as well as a highly specific property: a CCR5 Delta 32 mutation on the donor’s viral receptors that prevent HIV binding. On this project, the researchers aim to create genes that code for engineered CAR T-cells delivered with blood-forming stem cells when transplanted into people with HIV infections. Once in the bone marrow, the stem cells transform into CAR T-cells that prevent binding by HIV viruses. The team also plans to bolster these CAR T-cells with genetically engineered B-cells in the immune system that produce neutralizing antibodies targeting HIV, which the researchers say are being tested with monkeys to clear viruses similar to HIV.

“The overarching goal of our proposed studies,” says Kitchen in a UCLA statement, “is to identify a new gene therapy strategy to safely and effectively modifies a patient’s own stem cells to resist HIV infection and simultaneously enhance their ability to recognize and destroy infected cells in the body in hopes of curing HIV infection.”

In an earlier study, Kitchen, Chen, and colleagues designed CAR T-cells carried in blood-forming stem cells that attack and clear viruses similar to HIV in monkeys. Their findings show the engineered T-cells ended up in lymph tissue and gastrointestinal tracts of the monkeys, the sites where HIV viruses accumulate, preventing return of HIV infections for two years, the follow-up time of the study. In addition, CAR T-cells continued to be produced during this time without adverse effects to the animals.

The researchers believe the combination of engineered T-cells and neutralizing antibodies will lead to a cure for HIV infections, not just suppression of the virus, and provide a template for other disease therapies. “The development of this unique strategy,” notes Chen, “that allows the body to develop multiple ways to attack HIV could have an impact on other diseases as well, including the development of similar approaches targeting other types of chronic viral infections and cancers.”

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