Immunotherapy Targeting HIV Reservoirs

Research Question

CAR T cell therapy, which uses T cells that have been engineered to target specific proteins, has revolutionized the treatment of some blood cancers. Yet success in HIV has lagged and several challenges remain. For example, how can we ensure that the CAR T cells go to the areas where they are needed? Can we make them resistant to being killed by HIV? Is there a safe way to enable them to persist long enough to wipe out every last trace of the virus?

Findings

The researchers involved in this study recently demonstrated that HIV-specific CAR cells prepared from gene-modified stem cells were able to generate T cells capable of killing HIV-infected cells in the test tube. These modified cells were also able to reduce viral loads in monkeys infected with a simian/human immunodeficiency virus hybrid.

By making them from stem cells, these CAR T cells should be able to persist indefinitely as a renewable resource in the body.

In the current study, these cells were documented to travel to, and persist for at least two years in lymphoid tissues as well as the gut and brain, all of which are potential sites for HIV reservoirs.

Impact

The authors concluded that HIV-specific, stem cell-derived CAR T cells may be a promising approach to at least a “functional cure” for HIV—controlling the virus in the absence of antiretroviral therapy.

amfAR’s Role

amfAR was a funder of this study and has supported the work of Dr. Scott Kitchen since 2013 while he designed and tested these CAR cells. Dr. Kitchen is using these cells in amfAR’s ARCHE-GT consortium, as part of a combination gene therapy approach to curing HIV. 

Original Article

http://www.ncbi.nlm.nih.gov/pubmed/33427210

Dr. Laurence is amfAR’s senior scientific consultant and Dr. Johnston is vice president and director of research.

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