HEALTH NEWS

Researchers Look at CAR-T Treatments for HIV

Written by George Citroner on January 10, 2018

In a new study, the treatment that has shown promise in fighting cancer also was effective in battling the virus that causes AIDS.

hiv

A new treatment that has shown promise in defeating cancer might eventually also be effective in battling the virus that causes AIDS.

According to a published last month in PLOS Pathogens, genetically engineered chimeric antigen receptor (CAR) T cells might be used to ultimately eradicate HIV.

Scott Kitchen, PhD, and his colleagues at the University of California, Los Angeles believe that the key to eliminating HIV-infected cells is to use these specially modified cells to enhance the body’s immune response.

This study was restricted to animals and lab dishes, but researchers say the findings still open up the possibility that gene modification can be used to defeat HIV.

To produce the first gene therapy for cancer, scientists gave the T cells (a subtype of white blood cells) specific genes that create surface molecules (CARs) capable of recognizing and attaching to their counterparts on tumor cells. The CAR-T cells are then activated, allowing them to eliminate tumor cells.

HIV treatment a bigger challenge

This is more challenging for HIV because the virus also infects the T cells themselves by integrating its genes into the T cell’s DNA.

Researchers resolved this problem by modifying T cells to both resist infection and control HIV replication.

To produce T cells that can fight HIV, the T cells themselves aren’t modified. The alterations are made to the stem cells that make both T cells and other blood cells.

This genetic engineering gives the stem cells (and all their descendants) a CAR that’s HIV-specific.

A part of the CAR called CD4 can both find and bind with HIV. Another surface molecule, called C46, then interferes with the virus’ ability to enter T cells.

That creates T cells that can detect HIV without becoming infected. It also allows them to discover and eliminate the HIV-infected cells, which have some of the identical T-cell-attracting surface molecules as the AIDS virus.

In this study, the modified cells were produced for more than two years without any adverse events.

There was also a wide distribution of those cells in the digestive tract and lymphoid tissues. Both are major locations for HIV replication.

Potential barriers

This is the first time the safety and feasibility of immunotherapy has been demonstrated with an HIV-specific CAR for suppressing HIV infection.

“The biggest foreseeable barrier involves the transplantation procedures, which we are currently working to optimize,” Kitchen said in a statement. “However, there are numerous clinical trials ongoing that we can base many aspects of this on when we get to that stage. There were no significant safety issues that we have observed so far in the use of this CAR in a hematopoietic-stem-cell-based gene therapy.”

But, even if this method proves effective in humans, there’s no guarantee it will be used against HIV.

That’s because CAR-T therapy comes with a hefty price tag.

The company behind one CAR-T treatment is Novartis. They’re charging almost a half-million dollars for just treatment with Kymriah. That’s not including any other associated costs, as reported by .

However, Kitchen is confident researchers can solve the cost issue.

“Yes, we are working on issues such as dosing and optimizing transplantation procedures, which do not have to involve full immune ablation, and other ways to administer the CAR to hematopoietic (blood forming) stem cells in vivo,” he said. “These could make the procedure less invasive and less expensive to perform.”

He further states, “Our approach could allow individuals to wean off of or lessen their dependence on antiretroviral therapies, saving significant costs and reducing adherence issues and toxicities that are often associated with taking antiretroviral medication. We are working on ways to optimize this approach, to potentially reduce the cost of treatment.”

Looking ahead

Dr. William Schaffner, infectious disease specialist at Vanderbilt University, sees the potential for treatment of other infectious diseases.

“The implications for the treatment of both bacterial and viral infectious diseases like herpes, chicken pox, and antibiotic resistant tuberculosis are enormous,” Schaffner told Healthline.

He added that CAR-T is worth further investigation despite the expense and technical difficulties.

“Let research proceed full speed ahead, encourage the work,” Schaffner said. “We need to look at timelines further out than the next 5 to 10 years because CAR-T has so much potential.”

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