New Genetic Mechanism for Controlling Blood Cell Development and Blood Vessel Integrity Found

Source: University of Wisconsin-Madison
Date: September 10, 2012

Summary:

The protein GATA2 is known as a "master regulator" of blood cell development. When a mutation occurs in the gene that makes GATA2, serious blood diseases such as acute myeloid leukemia can result. Zooming in on the GATA2 gene, University of Wisconsin-Madison researchers and their collaborators at the National Institutes of Health (NIH) have discovered unexpectedly that a small DNA sequence drives this powerful master regulator. The sequence plays an essential role in controlling GATA2 production and generating self-renewing blood stem cells responsible for the earliest steps in the development of blood cells of all kinds — red cells to transport oxygen and white cells to fight infection.

The researchers also found that the DNA sequence, which they call the +9.5 GATA2 switch site, ensures that blood vessels function properly to prevent hemorrhaging. Until now, GATA2 had not been implicated in blood vessel integrity. The study appears in The Journal of Clinical Investigation (online Sept. 10, 2012).

Genetically Modified T Cell Therapy Shown to be Safe, Lasting in Decade-Long Penn Medicine Study of HIV Patients

Source: University of Pennsylvania School of Medicine
Date: May 2, 2012

Summary:

HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.

STUDY USING STEM CELL THERAPY SHOWS PROMISE IN FIGHT AGAINST HIV

Source: University of California - Davis Health System
Date: May 1, 2012

Summary:

(SACRAMENTO, Calif. — UC Davis Health System researchers are a step closer to launching human clinical trials involving the use of an innovative stem cell therapy to fight the virus that causes AIDS. In a paper published in the May issue of the Journal of Virology, the UC Davis HIV team demonstrated both the safety and efficacy of transplanting anti-HIV stem cells into mice that represent models of infected patients. The technique, which involves replacing the immune system with stem cells engineered with a triple combination of HIV-resistant genes, proved capable of replicating a normally functioning human immune system by protecting and expanding HIV-resistant immune cells. The cells thrived and self-renewed even when challenged with an HIV viral load.

Engineered Stem Cells Seek out and Kill HIV in Living Mice

Source: University of California, Los Angeles (UCLA), Health Sciences
Date: April 12, 2012

Summary:

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.

HIV Drug Reduces Graft-versus-Host Disease in Stem Cell Transplant Patients, Penn Study Shows

Source: University of Pennsylvania School of Medicine
Date: December 13, 2011

Summary:

(SAN DIEGO) -- An HIV drug that redirects immune cell traffic appears to significantly reduce the dangerous complication graft-versus-host disease (GvHD) in blood cancer patients following allogeneic stem cell transplantation (ASCT), according to new research from the Perelman School of Medicine at the University of Pennsylvania that will be presented today at the 53rd American Society of Hematology Annual Meeting. Standard GvHD treatments suppress the immune system, reducing – but not eliminating – the risk of developing the common problem. In the current trial, treatment with the HIV drug maraviroc dramatically reduced the incidence of GvHD in organs where it is most dangerous -- without compromising the immune system and leaving patients more vulnerable to severe infections.

Hutchinson Center to lead a $20 million research project to explore a potential cure for HIV infection

Source: Fred Hutchinson Cancer Research Center
Date: July 11, 2011

Summary:

SEATTLE — Whether a stem cell transplant using an HIV-infected person’s own genetically modified immune cells can become a cure for the disease is the focus of a new $20 million, five-year research grant award announced today by the National Institutes of Health to Fred Hutchinson Cancer Research Center. Hutchinson Center researchers will use the grant to lead a multifaceted team of scientists and institutions to study whether a person’s own stem cells can be engineered to deny HIV entry into the body’s blood cells. The researchers also will work to develop tools to eradicate existing reservoirs of infection in the body.

Researchers Create HIV-Resistant Cells

Source: University of Southern California
Date: July 6, 2010

Summary:

Researchers at the Keck School of Medicine of USC successfully have transplanted blood stem cells modified to be resistant to HIV into mice, allowing the animals to control HIV infections. If the approach can be translated to human patients, it would enable the long-term generation of HIV-resistant T cells in a patient’s body, and the potential for the patient’s own cells to suppress HIV. The strategy is explained in a new study published online in the journal Nature Biotechnology.

The approach targets a gene called CCR5, one of the two gateway molecules that HIV uses to enter human cells. Cannon’s strategy arose from the observation that people with a mutation in a gene called CCR5 are naturally resistant to infection with the most common strains of HIV and do not develop AIDS.

The team used enzymes called zinc finger nucleases — which physically cut DNA — to knock out the the CCR5 gene in human blood stem cells. The researchers transplanted these modified stem cells into mice, where they developed into mature cells of the human immune system, including the T cells that HIV infects. When the researchers then infected the animals with HIV, they found that the mice were able to maintain normal levels of the human T cells and suppress HIV to very low levels, unlike control mice that received unmodified stem cells.

Clinical trial of gene therapy for AIDS-related lymphoma shows promising results against cancer and HIV infection

Source: City of Hope
Date: June 16, 2010

Summary:

City of Hope researchers demonstrated the first successful long-term persistence of anti-HIV genes in patients with AIDS-related lymphoma. In the investigational therapy, patients underwent autologous hematopoietic cell transplantation (HCT) in which their own blood stem cells were harvested and genetically engineered with three anti-HIV ribonucleic acids (RNAs) that block HIV from infecting new cells. The study appears online June 16 in the journal Science Translational Medicine.

The gene therapy was developed by City of Hope’s John Rossi, Ph.D., Lidow Family Research Chair and chair and professor, molecular and cellular biology, with technology that uses ribozymes and short strands of RNA, also known as small interfering RNA (siRNA), to selectively silence specific genes against HIV infection. The ribozyme molecule prevents the patient’s white blood cells from producing a protein called CCR5, which HIV needs to enter a cell. The new CCR5-deficient immune cells the patient produces are effectively resistant to HIV infection. Additionally, the siRNA inactivates the virus directly, and a third component, called a TAR decoy sequesters the HIV regulatory Tat protein from the virus. The goal of the therapy is to reboot the immune system to once again identify HIV and mount a response to the infection by lowering the viral load.

Scientists identify reservoirs where HIV-infected cells can lie in wait

Source: University of Michigan Health System
Date: March 7, 2010

Summary:

ANN ARBOR, Mich. – University of Michigan scientists have identified a new reservoir for hidden HIV-infected cells that can serve as a factory for new infections. New research shows that bone marrow, previously thought to be resistant to the virus, can contain latent forms of the infection. The findings, which appear online today in Nature Medicine, indicate a new target for curing the disease so those infected with the virus may someday no longer rely on AIDS drugs for a lifetime and may open the door to new treatments. The new research also gives a broader view of how HIV overwhelms the body’s immune system and devastates its ability to regenerate itself.

Gene-based stem cell therapy specifically removes cell receptor that attracts HIV

Source: University of California - Los Angeles
Date: February 25, 2010

UCLA AIDS Institute researchers successfully removed CCR5 — a cell receptor to which HIV-1 binds for infection but which the human body does not need — from human cells. Individuals who naturally lack the CCR5 receptor have been found to be essentially resistant to HIV. Using a humanized mouse model, the researchers transplanted a small RNA molecule known as short hairpin RNA (shRNA), which induced RNA interference into human blood stem cells to inhibit the expression of CCR5 in human immune cells. The findings provide evidence that this strategy can be an effective way to treat HIV-infected individuals, by prompting long-term and stable reduction of CCR5. The results are being published in Blood, Journal of the American Society of Hematology.

Researchers demonstrate that stem cells can be engineered to kill HIV

Source: University of California - Los Angeles
Date: December 7, 2009

Summary:

Researchers from the UCLA AIDS Institute and colleagues have for the first time demonstrated that human blood stem cells can be engineered into cells that can target and kill HIV-infected cells — a process that potentially could be used against a range of chronic viral diseases. The study, published Dec. 7 in the-peer reviewed online journal PLoS ONE, provides proof-of-principle — that is, a demonstration of feasibility — that human stem cells can be engineered into the equivalent of a genetic vaccine.

World’s first engineered T cell receptor trial opens with new cellular therapy for HIV

Source: Adaptimmune Ltd. / University of Pennsylvania School of Medicine
Date: 7 October 2009

Summary:

Researchers at Adaptimmune Limited and the University of Pennsylvania School of Medicine, today announced the approval of an Investigational New Drug (IND) application from the US Food and Drug Administration (FDA) and opening for enrolment of the first ever study using patients’ cells carrying an engineered T cell receptor to treat HIV (SL9 HA-GAG-TCR). The trial may have important implications in the development of new treatments for HIV potentially slowing – or even preventing – the onset of AIDS.

Scientists find way to coax human stem cells into becoming T cells

Source: Sunnybrook Health Sciences Centre
Date: August 4, 2009

Summary:

Canadian researchers have developed a way to direct unspecified human stem cells into becoming progenitor (or early) T cells, which then go to the thymus and give rise to mature T cells, an essential ingredient in immune system reconstitution. This critical advance in regenerative medicine, published in the July 30 edition of Blood, makes possible new approaches to treating people with severe immune deficiencies, such as children born with little or no immune system, or people who have had chemotherapy. Scientists at Sunnybrook Research Institute created the human progenitor T cells from stem cells in the lab using a method that they patented. They then implanted them into immune-deficient mice, wherein the unspecified cells travelled to the thymus and produced mature T cells.

Stem cell treatment could fight AIDS

Source: Daily Telegraph
Last Updated: 17 January 2009 10:37 PM GMT

Summary:

The Daily Telegraph reports bone marrow stem cells improved the condition of patients with HIV after receiving the cells as part of a bone marrow transplant to treat lymphoma:

"Results of a preliminary trial have raised hopes of a new form of therapy for people suffering from Aids, which occurs in the latter stages of infection with Human Immunodeficiency Virus (HIV). The scientists are planning further research to establish whether the treatment could even rid patients of HIV infection altogether. The technique involves isolating genes which curb the spread of HIV inside the body, introducing the genes into human stem cells in a laboratory, then transplanting the stem cells into a patient's bone marrow."

"In the first human trial, anti-HIV stem cells were transplanted into five Aids patients undergoing bone marrow replacement as part of treatment for a form of cancer known as lymphoma. Small quantities of the transplanted stem cells were able to grow and produce new white blood cells resistant to HIV, resulting in an improvement in the patients' conditions."

Researchers Exploring Gene Therapy To Fight AIDS

Source: University of California - Davis
Date: December 5, 2008

Summary:

The apparent success of a case in which German doctors cured a man of AIDS using a bone marrow transplant comes as no surprise to Gerhard Bauer, a UC Davis stem cell researcher. Bauer has been working for more than 10 years on a similar cure for AIDS based on replacing the devastated immune system of an HIV-infected patient with stem cells that have been engineered to resist human immunodeficiency syndrome. Bauer plans to present the preliminary results of his latest research at the 50th annual meeting of the American Society for Hematology in San Francisco on Sunday, December 6, 2008, from 6 to 8 p.m. at the Moscone Center. He and his UC Davis research team will present a poster detailing the development of a mouse model that allows pre-clinical testing of their new gene-therapy protocol, which they hope will pave the way for human clinical trials within five years.

Scientists Uncover How HIV Hides Inside Cells

Source: HealthDay News
Posted: April 1, 2008; 12:00 AM EDT

Summary:

U.S. researchers say they've discovered how HIV -- the virus that causes AIDS -- hides in human cells to avoid being destroyed by the body's immune cells. They explained that when a normal virus, such as the common cold, infects a person, the immune system responds and produces cells that quickly eliminate the virus. However, HIV makes itself appear as part of the normal trash in a cell, rather than being clearly visible on the cell surface.

Insight into HIV's 'on-off' switch shows promise for therapy, understanding cellular decisions

Source: University of California - San Diego
Date: March 16, 2008

Summary:

Researchers at the University of California, San Diego and Oak Ridge National Laboratory have discovered how a genetic circuit in HIV controls whether the virus turns on or stays dormant, and have succeeded in forcing the virus towards dormancy, a finding that shows promise as an avenue for HIV therapy. Their findings are published in the March 16 issue of the journal Nature Genetics.

Researchers genetically engineer immune cells into potent weapons for battling HIV

Source: Albert Einstein College of Medicine
Date: March 4, 2008

Summary:

By outfitting immune-system killer cells with a new pair of genes, scientists at the Albert Einstein College of Medicine of Yeshiva University transformed them into potent weapons that destroy cells infected with HIV, the virus that causes AIDS. Their novel strategy of genetically engineering immune cells to redirect their infection-fighting ability toward killing HIV-infected cells could lead to an entirely new approach for combating AIDS and other viral diseases. The findings appear in the March issue of the Journal of Virology.

Yale Scientists Create Artificial “Cells” that Boost the Immune Response to Cancer

Source: Yale University
Date: February 26, 2008

Summary:

Using artificial cell-like particles, Yale biomedical engineers have devised a rapid and efficient way to produce a 45-fold enhancement of T cell activation and expansion, an immune response important for a patient’s ability to fight cancer and infectious diseases, according to an advance on line report in Molecular Therapy.

Experimental HIV vaccine gets a boost from ’70s-era discovery

Source: Rockefeller University
Date: February 13, 2008

Summary:

Although science is known for being a forward-looking field, researchers have found that they can often benefit from a glance over their shoulders. By combining an experimental AIDS vaccine with a long-neglected molecule called poly-IC, Rockefeller University scientists discovered that they were able to significantly improve its effectiveness. Their new, bolstered vaccine not only stimulated the production of HIV-attacking immune cells in mice, but also allowed the rodents to maintain immunity over a significantly longer period of time.