HIV controlled with improved CAR T therapy

A breakthrough cancer treatment is to be tested in patients next year for its original purpose, controlling HIV infection.

Researchers at the University of Pennsylvania, where its use in blood cancer was pioneered, say they’ve tweaked multiple facets of what is called CAR T cell therapy. It uses genetically engineered immune cells to fight disease targets.

The treatment earlier failed a clinical trial for HIV. The improved version is more than 50 times as effective in reducing HIV replication than the previous one, they say.

A study demonstrating the improved results was published Thursday in the journal PLOS Pathogens. James L. Riley was senior author. Rachel S. Leibman was the first author. Go to j.mp/carthiv for the study.

The improved therapy is planned for testing in a few patients beginning in the late spring of 2018, Riley said. It benefits from the work of scientists including University of Pennsylvania researcher Carl June, whose research led to the leukemia treatment, Kymriah, he said.

“It’s nice to have a benchmark by which you know this particular configuration works,” Riley said.

June had originally aimed to develop immune treatments for HIV, according to a perspective article on CAR T cell therapy in the New England Journal of Medicine. June shifted focus after his wife developed ovarian cancer in 1996. She died in 2001.

The therapy uses T cells, an important part of the immune system, genetically engineered to look for and attack cells that make specific proteins. The cells are extracted from the patient, given the therapeutic genes, allowed to proliferate, then re-infused into the patient.

In cancer, the immune system has trouble recognizing that the body’s own cells have become a danger to be eliminated. Chimeric antigen receptor, or CAR T cells are designed to overcome this problem.

Dr. Carl June discusses how the emerging discipline of synthetic biology - which combines elements of genetic engineering and molecular biology to create new biological structures with enhanced functionalities - can be applied to cancer. He also talks about the outlook for chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies, including managing toxicities and expanding the availability of personalized cell therapy for all hematologic malignancies and solid tumors.

Moreover, this therapy has the potential for providing permanent control. Some T cells persist even when the target is eliminated, ready to spring into action when needed. This is valuable in the case of cancer and HIV, diseases in which complete elimination of the disease is very difficult.

In the case of Kymriah, the CAR T cells look for a protein made by B cells, antibody-making immune cells that become cancerous in the form of leukemia the drug treats.

For HIV, the challenge is trickier, because the virus infects T cells themselves. It also integrates its own genetic code into the cellular DNA. To stop this, the researchers improved on the original engineered T cell to both better resist infection and control HIV replication.

The study is a “tour de force,” said Rowena Johnston, vice president and director of research at amFAR, The Foundation for Aids Research. The international nonprofit is dedicated to HIV/AIDS research, prevention and public policy.

“It was really a very thorough investigation, and very timely,” Johnston said. “It looked at a lot of the critical components of how we’re going to apply CAR T cell therapy in HIV.”

Johnston said she is optimistic that CAR T cell therapy will eventually be able to control HIV enough that those with the virus could rely on it alone, without needing other medicines.

However, totally eliminating the virus from the body, which would result in a cure, is much more challenging, she said. But one day, even a cure might be possible with this approach.

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