Personalized T cell therapy for HIV shows safety and early signs of impact

An exciting small clinical trial led by the Center for Cancer and Immunology Research at Children’s National Hospital has shown that a new HIV-specific T cell therapy is safe and may help reduce hidden reservoirs of the virus in the body. This approach, tested in six adults living with HIV, uses specially trained immune cells made from each person’s own blood — a personalized therapy designed to target the virus with precision.

The results, published in Nature Communications, represent a step forward in the search for a long-term, drug-free way to control or even cure HIV.

A smarter way to fight HIV

Today, people living with HIV rely on anti-retroviral therapy (ART) to keep the virus under control. These medications are highly effective but must be taken daily and do not eliminate the virus entirely. That is because HIV can hide in a “reservoir” of cells where it remains dormant and invisible to both drugs and the immune system. If ART is stopped, the virus can quickly return.

To change that, scientists at Children’s National and partnering institutions developed a new type of cellular therapy called HST-NEETs — short for “HIV-specific T cells targeting conserved epitopes”. These T cells are trained in the lab to recognize parts of the virus that do not change much, even as HIV mutates. This makes it harder for the virus to escape. The goal is to help the immune system find and destroy the infected cells that are normally hidden.

Safe and promising results

In this phase 1 clinical trial, researchers created personalized HST-NEET therapy from each participant’s own immune cells. After training the cells to recognize HIV, they were infused back into the patients twice over a period of weeks.

The results showed that:

• No serious side effects were reported from the infusions.
• The treatment was well-tolerated by all six participants.
• In two people, the therapy led to stronger HIV-specific immune responses, including more virus-fighting T cells and antibodies.
• In two others, researchers saw a drop in the level of HIV hidden in their cells, a sign that the virus reservoir might be shrinking.
• In four participants, the infused T cells persisted in the bloodstream for up to 40 weeks, continuing to patrol for signs of HIV.

While not a cure, these findings show early evidence that the therapy may help the body better recognize and fight HIV, even the hidden forms that are hardest to treat.

Building toward a cure

“The fact that we saw HIV-specific T cell responses increase in some participants, even without additional immune-boosting drugs, is very encouraging,” said Catherine Bollard, MBChB, MD, senior author of the study and director of the Center for Cancer and Immunology Research at Children’s National. “It suggests that the immune system can be trained to go after parts of the virus that were previously out of reach.”

Unlike bone marrow transplants, which have led to a cure in a few people with both HIV and cancer but carry high risk, HST-NEET therapy is much safer and more scalable. That is important for the millions of people living with HIV worldwide.

This study also sets the stage for future clinical trials that could combine T cell therapy with other strategies, like latency-reversing drugs that “wake up” hidden HIV, to further shrink the reservoir.  It also shows that personalized T cells can be safely made, infused and tracked over time and that they can continue working in the body for many months. Those lessons are valuable not just for HIV but also for developing safer, more targeted cancer immunotherapies in children and adults.

What’s next

The next phase of research will evaluate this therapy in larger groups and under different conditions, including in people undergoing stem cell transplants or with added immune system boosters. Clinical trials are already underway exploring these combinations.

By focusing on preserved parts of the virus, the regions that HIV cannot easily mutate, HST-NEETs could one day become part of a combination approach to eliminate HIV from the body altogether.

“Every step brings us closer to a functional cure,” said Dr. Bollard. “And the lessons we’re learning from HIV may also inform how we treat other chronic viral infections, and even cancer, in the future.”

Authors authors from Children’s National include Danielle K. Sohai, Michael D. Keller, Patrick J. Hanley, Fahmida Hoq, Divyesh Kukadiya, Anushree Datar, Emily Reynolds, Christopher Lazarski, Chase D. McCann, Jay Tanna, Abeer Shibli, Haili Lang, Anqing Zhang, Pamela A. Chansky, Cecilia Motta and Conrad Russell Y. Cruz.