CAR-T cell Therapy Is Expected to Resist HIV Infection

In a new study, researchers from Perelman College of Medicine, University of Pennsylvania, tried to develop a CAR T therapy that could potentially be used to genetically modify patients' own immune system cells as a new strategy to fight against HIV, showing benefits in mouse and in vitro cultured human cells.

Leukocytes, called T cells, play an important role in the immune response to HIV in the immune system, especially if the patient stops taking antiretroviral drugs (ART), which cause this disease under control. However, HIV still figures out several methods to avoid T cell attack. As a result, some scientists have proposed to genetically modify the patient's own T cells to fight HIV more effectively.

People used to attempt to fight against HIV by genetically modifying T cells, including one that has undergone clinical trials. However, until now, no method has been applied successfully. Today, Rachel Leibman, a Ph.D. student at the Perelman Medical School at the University of Pennsylvania, and his colleagues carry out a promising trial, which is established on the earlier approach with clinical trials. This earlier approach relies on the chimeric antigen receptor (CAR), a synthetic protein that, when introduced into T cells, allows them to resist specific enemies more effectively. During the treatment, T cells extracted from the blood of a patient were genetically modified in the laboratory to express HIV-specific CARs, which were then infused back into the patient to fight off the virus.

Taking advantage of the recent advances in CAR T technology, Leibman and her colleagues have improved on this CAR protein that has previously been clinically tested (ie, initial CAR). This protein consists of several different segments, so they systematically tailor the proteins to optimize their performance. They found that T cells that express this new CAR are more than 50-fold more effective in stopping the virus from spreading in human cells than in T cells expressing initial CARs in the laboratory.

The researchers also tested this new type of CAR in mice infected with HIV. They found that mouse T cells genetically modified to express this new CAR, which was able to protect other T cells in these mice from HIV attack and rejection. In mice treated with antiretroviral therapy, these genetically modified T cells delay the virus rebound after the treatment is stopped.

These findings may pave the way for the clinical trials of this enhanced new CAR T therapy to genetically modify T cells. If successful, this approach could potentially put HIV under control without antiretroviral treatment. The researchers explained, "Our data show for the first time that genetically modified T cells can dramatically control the virus rebound without ART treatment, and our next step is moving to clinical trials."