Can Stem Cells Cure HIV?

Can stem cells cure HIV? Yes, that’s possible — if clinical trials planned by a team of scientists from the University of California in Los Angeles (UCLA) push through in the future, and succeed.

If these prove successful, a breakthrough technique they developed — of genetically engineering stem cells into “warrior” cells that fight HIV — could lead to biologic treatments that could be available to patients in about ten years.

A retrovirus of two strains — HIV-1 or HIV-2 — HIV or human immunodeficiency virus — destroys the immune system’s helper T cells. This loss of T cells causes the dreaded disease, acquired immunodeficiency syndrome (AIDS) that leaves a person vulnerable to life-threatening infections.

Previous HIV research focused mostly on developing vaccines or drugs aimed to slow the virus’s progression. Now, an exciting medical breakthrough comes from a series of studies conducted by the UCLA researchers. Taken together, the findings of all their pioneering studies mean that there’s now a good chance that a potential biologic treatment can be developed to eradicate HIV completely from an infected patient.

In their most recent study, published in the April 12 issue of the journal PLoS Pathogens, the UCLA investigators show that human stem cells can be genetically engineered to turn into “killer” cells that seek out and kill HIV-infected cells in a living organism. The genetically engineered cells have also proven to be effective in suppressing the virus in lab mice.

This is the first time that stem cells — genetically engineered to form immune cells that target HIV — have been shown to be effective in suppressing the virus in an animal’s living tissues, says lead researcher Dr. Scott G. Kitchen, an assistant professor of medicine in the hematology and oncology division at UCLA’s David Geffen School of Medicine. Dr. Kitchen is also 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,” Dr. Kitchen says in a statement.

Desperate need for new approaches to AIDS epidemic
In the 31 years since it was first recognized by the United States Centers for Disease and Prevention in 1981, HIV/AIDS has reached epidemic proportions. Today, about 34 million adults worldwide live with HIV/AIDS and the World Health Organization says most will die from the opportunistic infections that develop in their now vulnerable bodies — despite improved access to antiretroviral treatment and care in many parts of the world. At least 3.4 million children live with HIV/AIDS and 16.6 million children have been left orphaned by the dreaded disease.

This is why there’s a desperate need for new approaches to eradicate HIV. But the virus actively subverts the powerful response that a body’s immune system mounts against it. It does this by foiling cellular cytotoxic T lymphocyte (CTL) responses. CTLs — or “killer” T cells — are a type of white blood cell that kill the cells infected with viruses and other pathogens. To do this, they have to carry a particular molecule — a receptor — that helps them locate and destroy the target pathogen.

In their research, Dr. Kitchen and his team sought to find a way to contain HIV — as well as restore and boost the CTL response sufficiently to eradicate the HIV in the body.

Genetically engineering stem cells
In their previous study, the researchers took CTLs from an HIV-infected person and found that these did have an HIV-targeting T-cell receptor that’s able to eliminate HIV-infected cells — but not in numbers sufficient enough to be able to clear HIV from the body.

What the UCLA researchers did next was this: They cloned the HIV-targeting T-cell receptor and used it to genetically engineer human hematopoietic stem cells or HSCs so that they would be destined to mature into working CTLs that kill HIV-infected cells.

They then put the genetically engineered stem cells into human thymus tissue that had been implanted into lab mice. This allowed them to investigate the reaction in a living organism — and this is what they found: The stem cells matured into a large population of multifunctional HIV-specific T-cells capable of targeting cells containing HIV proteins. Incidentally, the researchers also discovered that — in the way an organ has to be matched to a transplant patient — HIV-specific T cell receptors also have to be matched to the person who will receive them.

For the current study, the UCLA investigators again genetically engineered human blood stem cells, but this time, the genetically engineered cells were injected into a “humanized mouse.” Specifically this was called “a modified version of a humanized mouse model known as the non-obese diabetic (NOD)-SCID, common gamma chain knockout (γc−/−), humanized bone marrow, fetal liver, and thymus (the NSG-BLT) mouse model” — or a lab mouse modified to resemble the progression of AIDS in humans.

They found that the engineered stem cell could form mature T cells that can attack HIV in tissues where the virus resides and replicates.

Next, to check if the T-cells were working effectively, the researchers ran a series of tests on the “humanized mice” — checking their peripheral blood, plasma and organs at two weeks and six weeks after introducing the engineered cells.

Normally, following an HIV infection, a person experiences a drop in CD4, a group of white blood cells that also help fight off infections. But in contrast, what the researchers found was that the number of CD4 “helper” T cells had increased. Meanwhile, levels of HIV in the blood decreased.

These results indicate that the engineered cells were capable of developing and migrating to the organs to fight infection there, the researchers write in their report in the ‘PLoS Pathogens’ journal reported.

“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,” Dr. Kitchen says.

“We haven’t fully developed the technology to clear them of HIV, but they are significantly suppressed in the amount of virus that’s replicating,” he adds.

The UCLA investigators admit a potential weakness in their study: Because human immune cells reconstituted better at a lower level in the humanized mice than in humans, the mice’s immune systems were almost — but not completely — reconstructed.

But in HIV-infected people, HIV is mutates faster than it does in mice or humanized mice. This means that the use of multiple, engineered T cell receptors may be more effective against the faster and higher level of HIV mutations in humans. And that’s, in fact, what the researchers are now doing — they’re already working on making T-cell receptors that target different parts of the HIV that could be used in genetically matched individuals.

The team says human clinical trials aren’t far off — and a treatment for HIV may be just 10 years away.

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