Newswise UCLA researchers and colleagues have received a $13.65 million grant from the National Institutes of Health to investigate and further develop an immunotherapy known as CAR T, which uses genetically modified stem cells to target and destroy HIV.
The five-year grant, part of an NIH effort to develop gene-engineering technologies to cure HIV/AIDS, will fund a collaboration among UCLA; CSL-Behring, a biotechnology company in the United States and Australia; and the University of WashingtonFred Hutchinson Cancer Research Center.
Scott Kitchen, an associate professor of medicine in the division of hematology and oncology, and Irvin Chen, director of theUCLA AIDS Instituteat theDavid Geffen School of Medicine at UCLA,are leading the effort. The project will build on their previous research using CAR T therapy to combat the virus, which is constantly mutating and difficult to beat.
The overarching goal of our proposed studies is to identify a newgene therapy strategy to safely and effectively modify a patients own stem cells to resist HIV infection andsimultaneously enhance their ability to recognize and destroy infected cells in the body in hopes of curing HIV infection, said Kitchen, who also directs the humanized mouse core laboratory for UCLAsCenter for AIDS ResearchandJonsson Comprehensive Cancer Center.It is a huge boost to our efforts at UCLA and elsewhere to find a creative strategy to defeat HIV.
The only known cure of an HIV-infected person was announced in 2008. The famous Berlin patient received a stem cell transplant from a donor whose cells naturally lacked a crucial receptor that HIV binds to in order to kill cells and destroy the immune system. The main problems with this approach, the researchers say, are that the donor and recipient have to be highly matched often a rare event and that it often fails to produce a sufficient amount of HIV-protected cells that can clear the virus from the body.
Transplantation of blood-forming stem cells has been the only treatment strategy that has resulted ina functional cure for HIV infection, Kitchen said. Over 13 years after the first successfully cured HIV-infected patient, there is a substantial need to develop strategies that are capable of being used on everyone with HIV infection.
One of those strategies, CAR T, has been the subject ofongoing researchat UCLA by Chen, Kitchen and others. This approach involves genetically engineering a patients own blood-forming stem cells to carry genes for chimeric antigen receptors, or CARs. Once these stem cells are modified and transplanted back into the patient, they form specialized infection-fighting white blood cells known as T cells in this case, CAR T cells that specifically seek out and kill HIV-infected cells. In a recent study, the UCLA scientists found that engineered CAR T cells not only destroyed infected cells but also lived for more than two years the length of the study.
The thinking behind the NIH-funded project, the researchers say, is that a combination of CARs and broadly neutralizing antibodies may be a long-lasting, perhaps permanent, cure for HIV.
Our work under the NIH grant will provide a great deal of insight into ways the immune response can be modified to better fight HIV infection, said Chen, who is a professor of medicine and of microbiology, immunology and molecular genetics at the Geffen School of Medicine. The development of this unique strategy 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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UCLA receives nearly $14 million from NIH to investigate gene therapy to combat HIV - Newswise
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