Revamped CAR-T could curb HIV levels without antiretroviral drugs

Electromicrograph showing an HIV-infected T cell in blue and yellow
Previous attempts to use CAR-T therapy to fight HIV have not been effective enough for widespread use. A team led by University of Pennsylvania researchers modified different parts of a synthetic CAR protein to boost its efficacy. (NIAID)

While antiretroviral drugs effectively keep HIV at very low levels, they do not eliminate the virus. If a patient is taken off treatment, or doesn’t stick to his or her drug regimen, virus levels can quickly bounce back.

An approach involving chimeric antigen receptor (CAR) T cells could be the answer to containing HIV spread in the absence of antiretroviral therapy.

Adding a synthetic CAR protein to T cells makes them better able to fight a specific target, such as cancer or HIV. CAR-T therapy involves extracting a patient’s T cells, re-engineering them in a lab to express specific CAR proteins and then injecting the beefed-up T cells back into the patient.

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CAR-T technology came to the forefront in August, when Novartis won approval for Kymriah, the first such therapy to treat some patients with lymphoma. Kite Pharma is expected to gain FDA approval for its CAR-T cancer treatment soon. Using engineered T cells to fight HIV is not a new idea, but previous attempts have seen limited success.

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While a Ph.D. candidate at the University of Pennsylvania’s Perelman School of Medicine, Rachel Leibman worked to improve an existing CAR-T treatment. Her team “systematically tweaked” various parts of the CAR protein, including the vector backbone and signaling domains, to boost the T cells’ ability to control HIV replication.

Testing it in the lab, they found it was 50 times more effective than the original CAR in preventing viral spread between human cells. The new and improved CAR-T cells staved off a rebound of HIV levels in mice that had been taken off antiretrovirals and also protected the mice’s T cells from being depleted by the virus.

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The data, which appear in PLOS Pathogens, suggest that a CAR-T approach could provide “durable control” of HIV without the need for antiretrovirals. The researchers plan to bring the concept into the clinic.

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Scientists have long sought a cure for HIV, but the virus remains a tricky foe. Because it can hide itself in infected cells, it is difficult to tell if a patient is truly cured. A University of Pittsburgh team devised a test that quickly spots dormant and replicating HIV, while University of Montreal researchers have tried inhibiting the mTOR pathway to prevent HIV from replicating in the gut.

Gene editing could be a possible treatment too. A Temple University team safely used CRISPR to edit HIV out of the genome of human T cells last year. Excision BioTherapeutics, which recently picked up $10 million in seed funding, was founded on this research. Following promising results in mouse models, the company intends to start human testing of its CRISPR-based treatment.