Reengineered immune system cells show early promise against HIV

October 12, 2017
HIV-infected T cell. Scanning electromicrograph of an HIV-infected T cell. Credit: NIAID

Improving on a previous attempt, scientists have developed a new strategy that could potentially be used to reengineer a patient's own immune system cells to fight HIV. The approach, described in PLOS Pathogens, shows benefit in human cell cultures and in mice.

White blood cells known as T cells play an important role in the immune system's response to HIV infection, especially if a patient stops taking antiretroviral medications that normally keep the disease under control. However, HIV has several strategies it can use to evade T-cell attack. Therefore, some researchers have proposed reengineering a patient's own T cells to more effectively fight HIV.

Several attempts to reengineer T cells to fight HIV have been made in the past, including one approach that made it to clinical testing. However, none have yet been successful enough for widespread use. Now, a new attempt by Rachel Leibman, a PhD candidate in the Perelman School of Medicine at the University of Pennsylvania, and colleagues shows promise.

The new technique builds on the earlier approach that made it to clinical trials, which relied on a chimeric antigen receptor (CAR)—a synthetic protein that when added to T cells allows them to fight a specific foe more effectively. In treatment, T cells extracted from a patient's blood would be reengineered in the lab to express HIV-specific CARs, and then infused back into the patient to fight the virus. (Other CAR-based techniques successfully enhance T cell attack of some .)

Using recent advances in CAR technology, Leibman and her colleagues enhanced the CAR protein that had previously made it to clinical testing. The protein consists of several different segments, which the scientists systematically tweaked one by one to optimize their performance. They found that T cells expressing the new CAR were over 50 times more effective than those with the original CAR in preventing viral spread between in the lab.

The researchers also tested the new CAR in mice infected with HIV. They found that mouse T cells reengineered to express the new CAR could protect other T cells in the mice from being attacked and depleted by HIV. In mice that had been receiving antiretroviral treatment, the reengineered T cells delayed rebound of the virus after treatment was stopped.

These findings could pave the way to clinical testing of T-cell reengineering using the new, enhanced CAR. If successful, such an approach could potentially keep HIV under control in the absence of .

"Our data shows for the first time that engineered T can significantly control viral rebound in the absence of ART in vivo," the authors explain. "Our next step is to take this concept forward into the clinic."

Explore further: Synthetic molecule 'kicks and kills' some persistent HIV in mice

More information: Leibman RS, Richardson MW, Ellebrecht CT, Maldini CR, Glover JA, Secreto AJ, et al. (2017) Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor. PLoS Pathog 13(10): e1006613. doi.org/10.1371/journal.ppat.1006613

Related Stories

Synthetic molecule 'kicks and kills' some persistent HIV in mice

September 21, 2017
Scientists have designed a synthetic molecule that can reactivate dormant human immunodeficiency virus (HIV) in mice and lead to the death of some of the infected cells, according to a study published in PLOS Pathogens.

Cell mechanism discovery could lead to 'fundamental' change in leukaemia treatment

July 27, 2017
Researchers have identified a new cell mechanism that could lead to a fundamental change in the diagnosis and treatment of leukaemia.

Depleting CAR T cells after tumor treatment reverses B cell deficiency in mice

October 17, 2016
Genetically engineered T cells, or CAR T cells, represent a promising approach to treat multiple types of cancer. These therapies can eliminate tumors by targeting specific markers that are expressed on different cancer cell ...

Researchers chart pathway to 'rejuvenating' immune cells to fight cancers and infections

June 27, 2017
St. Jude Children's Research Hospital immunologists have discovered how immune cells called T cells become "exhausted"—unable to do their jobs of attacking invaders such as cancer cells or viruses. The finding is important ...

Protein that activates immune response harms body's ability to fight HIV

December 23, 2016
In findings they call counterintuitive, a team of UCLA-led researchers suggests that blocking a protein, which is crucial to initiating the immune response against viral infections, may actually help combat HIV.

Artificial thymus can produce cancer-fighting T cells from blood stem cells

April 4, 2017
UCLA researchers have created a new system to produce human T cells, the white blood cells that fight against disease-causing intruders in the body. The system could be utilized to engineer T cells to find and attack cancer ...

Recommended for you

Gene therapy improves immunity in babies with 'bubble boy' disease

December 9, 2017
Early evidence suggests that gene therapy developed at St. Jude Children's Research Hospital will lead to broad protection for infants with the devastating immune disorder X-linked severe combined immunodeficiency disorder. ...

In lab research, scientists slow progression of a fatal form of muscular dystrophy

December 8, 2017
In a paper published in the Nature journal Scientific Reports, Saint Louis University (SLU) researchers report that a new drug reduces fibrosis (scarring) and prevents loss of muscle function in an animal model of Duchenne ...

Double-blind study shows HIV vaccine not effective in viral suppression

December 7, 2017
(Medical Xpress)—A large team of researchers from the U.S. and Canada has conducted a randomized double-blind study of the effectiveness of an HIV vaccine and has found it to be ineffective in suppressing the virus. In ...

Time matters: Does our biological clock keep cancer at bay?

December 7, 2017
Our body has an internal biological or "circadian" clock, which cycles daily and is synchronized with solar time. New research done in mice suggests that it can help suppress cancer. The study, publishing 7 December in the ...

Novel harvesting method rapidly produces superior stem cells for transplantation

December 7, 2017
A new method of harvesting stem cells for bone marrow transplantation - developed by a team of investigators from the Massachusetts General Hospital (MGH) Cancer Center and the Harvard Stem Cell Institute - appears to accomplish ...

Inhibiting TOR boosts regenerative potential of adult tissues

December 7, 2017
Adult stem cells replenish dying cells and regenerate damaged tissues throughout our lifetime. We lose many of those stem cells, along with their regenerative capacity, as we age. Working in flies and mice, researchers at ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.