UCLA-engineered stem cells seek out and kill HIV in living organisms

Expanding on previous research providing proof-of-principal that human stem cells can be genetically engineered into HIV-fighting cells, a team of UCLA researchers have now demonstrated that these cells can actually attack HIV-infected cells in a living organism.

The study, published April 12 in the journal PLoS Pathogens, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model, said lead investigator Scott G. Kitchen, an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute.

"We believe that this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body," he said.

In the previous research, the scientists took CD8 cytotoxic T lymphocytes - the "killer" T cells that help fight infection - from an HIV-infected individual and identified the molecule known as the T cell receptor, which guides the T cell in recognizing and killing HIV-infected cells. However, these T cells, while able to destroy HIV-infected cells, do not exist in great enough quantities to clear the virus from the body. So the researchers cloned the receptor and used this to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.

The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.

In this current study, the researchers similarly engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates. They did so by using a surrogate model, the humanized mouse, in which HIV infection closely resembles the disease and its progression in humans.

In a series of tests on the mice's peripheral blood, plasma and organs conducted two weeks and six weeks after introducing the engineered cells, the researchers found that the number of CD4 "helper" T cells - which become depleted as a result of HIV infection - increased, while levels of HIV in the blood decreased. CD4 cells are white blood cells that are an important component of the immune system, helping to fight off infections. These results indicated that the engineered cells were capable of developing and migrating to the organs to fight infection there.

The researchers did note a potential weakness with the study: Human immune cells reconstituted at a lower level in the humanized mice than they would in humans, and as a result, the mice's immune systems were mostly, though not completely, reconstructed. Because of this, HIV may be slower to mutate in the mice than in human hosts. So the use of multiple, engineered T cell receptors may be one way to adjust for the higher potential for HIV mutation in humans.

"We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people," Kitchen said.

The researchers will now begin making T cell receptors that target different parts of HIV and that could be used in more genetically matched individuals, he said.

Other study authors are Bernard R. Levin, Gregory Bristol, Valerie Rezek, Sohn Kim, Christian Aguilera-Sandoval, Arumugam Balamurugan, Otto O. Yang and Jerome A. Zack, all of UCLA.

The National Institutes of Health, the California HIV/AIDS Research Program, the California Institute for Regenerative Medicine, the UC Multicampus Research Program and Initiatives from the California Center for Antiviral Drug Discovery, and the UCLA Center for AIDS Research (CFAR) funded this study.

The UCLA AIDS Institute, established in 1992, is a multidisciplinary think tank drawing on the skills of top-flight researchers in the worldwide fight against HIV and AIDS, the first cases of which were reported in 1981 by UCLA physicians. Institute members include researchers in virology and immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social sciences, public health, nursing and disease prevention. Their findings have led to advances in treating HIV, as well as other diseases, such as hepatitis B and C, influenza and cancer.

Most Popular Now

Sanofi to acquire Ablynx for €3.9 Billion

Sanofi and Ablynx, a biopharmaceutical company engaged in the discovery and development of Nanobodies®, entered into a definitive agreement under which Sanofi will offer ...

Repurposed drug found to be effective against Zika…

In both cell cultures and mouse models, a drug used to treat Hepatitis C effectively protected and rescued neural cells infected by the Zika virus - and blocked transmiss...

More stroke patients may receive crucial treatment…

More patients could be eligible for critical treatments to remove or dissolve blood clots that cause strokes, according to a new treatment guideline issued by the America...

In wine, there's health: Low levels of alcohol goo…

While a couple of glasses of wine can help clear the mind after a busy day, new research shows that it may actually help clean the mind as well. The new study, which appe...

Drug trial protocol redactions by industry sponsor…

New research published by the Journal of the Royal Society of Medicine exposes the extent of redactions in protocols for industry-sponsored randomised drug trials. Trial ...

Advanced Accelerator Applications receives FDA ap…

Novartis AG (NYSE: NVS) announced that Advanced Accelerator Applications, a subsidiary of Novartis Groupe S.A., has received US Food and Drug Administration (FDA) approva...

Interim publications of randomized trials make new…

Early results from randomized trials are sometimes published before the trial is completed. The results of such interim publications may generate a great deal of interest...

Blood vessel-on-a-chips show anti-cancer drug effe…

Researchers at the Institute of Industrial Science (IIS), the University of Tokyo, CNRS and INSERM, report a new organ-on-a-chip technology for the study of blood vessel ...

FDA approves new treatment for certain digestive t…

The U.S. Food and Drug Administration today approved Lutathera (lutetium Lu 177 dotatate) for the treatment of a type of cancer that affects the pancreas or gastrointesti...

Roche reports good results in 2017

In 2017, Group sales rose 5% to CHF 53.3 billion. Core operating profit grew 3% and Core EPS increased 5%, reflecting the good underlying business performance. On an IFRS...

Cells of 3 advanced cancers die with drug-like com…

Researchers at Southern Methodist University have discovered three drug-like compounds that successfully reverse chemotherapy failure in three of the most commonly aggres...

Pfizer announces positive top-line results for pot…

Pfizer Inc. has announced that REFLECTIONS B3281006, a comparative safety and efficacy study of PF-05280586 versus MabThera® (rituximab-EU), met its primary endpoint. PF-...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]