Paula Cannon. (USC Photo/Richard Carrasco)
An HIV research program led by scientists at USC and the Fred Hutchinson Cancer Research Center in Seattle has received a five-year, $14.6million grant from the National Institutes of Health. The team is advancing a gene therapy approach to control the virus without the need for daily medicines.
The programs co-directors are Paula Cannon, PhD, Distinguished Professor of Molecular Microbiology and Immunology at the Keck School of Medicine of USC, and Hans-Peter Kiem, MD, PhD, the Stephanus Family Endowed Chair for Cell and Gene Therapy at Fred Hutch. Other key partners are David Scadden, MD, a professor at Harvard University, and the biotechnology company Magenta Therapeutics.
The NIH award will support preclinical studies that combine gene editing against HIV with technologies for safer and more effective hematopoietic stem cell transplants. Such transplants, also known as bone marrow transplants, are currently used for severe blood cancers. They renew a patients immune system, which can be damaged by cancer therapies, by infusing healthy donor blood stem cells that can grow into any type of blood or immune cell.
The researchers goal is to build a therapy that prepares patients for a stem cell transplantation using their own cells with little to no toxicity, engineers their own stem cells to fight HIV and stimulates those cells to quickly produce new and engineered immune cells once theyre reintroduced into the patient.
This grant funds a team with an overarching goal of developing what our perfect HIV gene therapy would look like, Cannon said. All of these pieces could happen separately, but the fact that the NIH has funded us as a team means that the sum will be so much bigger than the parts.
Halting HIV without daily drugs
About 38million people worldwide are living with HIV, the virus that causes AIDS. HIV is manageable with daily antiretroviral drugs, but the research team seeks a more durable solution.
Their strategy is inspired by the three cases where patients seem to have been cured of HIV. All had aggressive leukemia and received blood stem cell transplants from donors who also carried a mutation that confers immunity to HIV. The mutation was in the CCR5 gene, which encodes a receptor that HIV uses to infect immune cells and is present in about 1 percent of the population.
Timothy Ray Brown, famously nicknamed the Berlin patient, received such a transplant in 2007; he has been off antiretroviral drugs since then, and the virus remains undetectable in his system. In recent years, patients in London and Dusseldorf have shown similar results.
I think of the Berlin patient as proof of principle that replacing the immune system with one thats HIV-resistant by removing CCR5 is a possible way to treat somebody, Cannon said.
However, the rigors of the blood stem cell transplant process, combined with the difficulty in finding tissue-matched CCR5-negative donors, make it highly unlikely that this will provide more than a very rare treatment.
Three for one gene therapy
The research team will tackle these two major problems. First, to get around the lack of CCR5-negative donors, Cannon has already helped pioneer the use of gene editing to remove CCR5 from a patients own stem cells. This is now an investigational treatment for HIV in a clinical trial at City of Hope in Duarte, California.
She will now combine CCR5 disruption with additional genetic changes, so that the progeny of engineered stem cells will release antibodies and antibody-like molecules that block HIV.
Our engineered cells will be good neighbors, Cannon said. They secrete these protective molecules so that other cells, even if they arent engineered to be CCR5-negative, have some chance of being protected.
Meanwhile, Kiems group is providing a third approach by adapting an emerging cancer treatment called CAR T cell therapy. This re-engineers T cells of the immune system with chimeric antigen receptors (CARs), which are customized to recognize cancer cells.
In this project, Kiem and colleagues will create stem cells whose T cell descendants can instead hunt down HIV-infected cells.
A gentler blood stem cell transplant
The grant also supports two other components that relate to the blood stem cell transplant.
Magenta Therapeutics is developing less-toxic protocols for conditioningpreparing a patients bone marrow to receive a transplant. Traditionally, mild chemotherapy or radiotherapy is needed to make room for newly infused stem cells and to help them re-engraft.
The company is instead using antibody-drug conjugates to deliver this conditioning much more narrowly and to reduce the side effects that occur with systemic chemo or radiation.
Meanwhile, Scadden and his team are addressing another drawback of stem cell transplants and conditioning, the delay before infused stem cells generate new immune cells in sufficient numbers. In cancer patients, this delay leaves them highly susceptible to infection.
Scadden is approaching this using an injectable gel that biochemically resembles the bone marrow environment, to quickly repopulate the immune system with HIV-fighting cells.
With success, the teams research may free HIV patients from the need for daily medication and the expense and potential side effects that come with it. Their work may also improve other therapies based on blood stem cells, for conditions such as cancer, sickle cell disease and autoimmune disorders.
A home run would be that we completely cure people of HIV, Cannon said. What Id be fine with is the idea that somebody no longer needs to take anti-HIV drugs every day because their immune system is keeping the virus under control, so that it no longer causes health problems and, importantly, they cant transmit it to anybody else.
By Wayne Lewis
Read more:
Gene therapy research for HIV awarded $14.6 million NIH grant - USC News
- SIRA: Could Stem Cell Therapy Renew Your Body Cells? - Private ... [Last Updated On: April 23rd, 2011] [Originally Added On: April 23rd, 2011]
- Stem Cell Series: Part 1 [Last Updated On: August 4th, 2011] [Originally Added On: August 4th, 2011]
- Huntington's Disease: Stem Cell Treatment Strategies at UC Davis [Last Updated On: August 4th, 2011] [Originally Added On: August 4th, 2011]
- Tianjin heart hospital the largest in Asia with stem cell treatment as well.mp4 [Last Updated On: August 4th, 2011] [Originally Added On: August 4th, 2011]
- Researchers hope stem cell treatment can improve heart healing [Last Updated On: August 4th, 2011] [Originally Added On: August 4th, 2011]
- Testimonial for Fetal Stem Cell Treatment of Duchenne Muscular Dystrophy [Last Updated On: August 5th, 2011] [Originally Added On: August 5th, 2011]
- MS Views and News Podcast - Stem Cell Treatment [Last Updated On: August 6th, 2011] [Originally Added On: August 6th, 2011]
- Duchenne's Muscular Dystrophy Stem Cell Treatment - Reelabs India [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- Stem cell treatment for Macular Degeneration - Graham Leach [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- The New World of Medicine: Stem Cell Therapy [Last Updated On: August 8th, 2011] [Originally Added On: August 8th, 2011]
- Stem Cell Treatment for Cerebral Palsy (Periventricular Leukomalacia) [Last Updated On: August 8th, 2011] [Originally Added On: August 8th, 2011]
- Medra Inc - Breakthrough Stem Cell Treatment [Last Updated On: August 9th, 2011] [Originally Added On: August 9th, 2011]
- Patricia VS Autism: Adult Stem Cell Treatment Part 1 [Last Updated On: August 10th, 2011] [Originally Added On: August 10th, 2011]
- Stem Cell Treatment for Multiple Sclerosis - Community Outreach San Diego: Xenia C. [Last Updated On: August 10th, 2011] [Originally Added On: August 10th, 2011]
- Stem Cell Treatment for Cerebral Palsy at the XCell-Center in Germany [Last Updated On: August 11th, 2011] [Originally Added On: August 11th, 2011]
- Bone Marrow Aspiration - Stem Cell Therapy [Last Updated On: August 13th, 2011] [Originally Added On: August 13th, 2011]
- Dr. William Rader - Breakthrough Stem Cell Treatment [Last Updated On: August 13th, 2011] [Originally Added On: August 13th, 2011]
- Clinical Advances in Adult Stem Cell Therapy - Dr. Jorge Paz Rodriguez (Miami) [Last Updated On: August 14th, 2011] [Originally Added On: August 14th, 2011]
- Stem cell treatment on horse a success, vet says [Last Updated On: August 15th, 2011] [Originally Added On: August 15th, 2011]
- Patricia VS Autism: Adult Stem Cell Treatment Part 2 [Last Updated On: August 15th, 2011] [Originally Added On: August 15th, 2011]
- Adult Stem Cell Therapy Clinical Advances - Dr. Jorge Paz in San Diego, CA March 2011 [Last Updated On: August 17th, 2011] [Originally Added On: August 17th, 2011]
- Dr. Ulrich Friedrichson, Geneticist, and Stem Cell Therapy pioneer [Last Updated On: August 19th, 2011] [Originally Added On: August 19th, 2011]
- Bone Marrow Stem Cells/Gene Therapy [Last Updated On: August 19th, 2011] [Originally Added On: August 19th, 2011]
- Regenerative Medicine With Stem Cell Therapy Injections at an Arizona pain clinic (602) 507-6550 [Last Updated On: August 19th, 2011] [Originally Added On: August 19th, 2011]
- Diabetes - Stem Cell Treatment [Last Updated On: August 21st, 2011] [Originally Added On: August 21st, 2011]
- Stem Cell Treatments for Autism: Community Outreach Miami, Florida - Juliana Ubinas [Last Updated On: August 22nd, 2011] [Originally Added On: August 22nd, 2011]
- Post Stem Cell Therapy Testimony of Cerebral Palsy [Last Updated On: August 26th, 2011] [Originally Added On: August 26th, 2011]
- VetCell's StemRegen - the original and best stem cell therapy for equine tendon injuries [Last Updated On: August 26th, 2011] [Originally Added On: August 26th, 2011]
- Stem cell treatment cures blind girl. More at http://www.stemcellfusion.com [Last Updated On: August 30th, 2011] [Originally Added On: August 30th, 2011]
- ALS Patient Interview, Stem Cell Treatments and ALS www.stemcellregenmed.com [Last Updated On: September 1st, 2011] [Originally Added On: September 1st, 2011]
- Stem Cell Treatment for Rheumatoid Arthritis - "I got my life back" [Last Updated On: September 1st, 2011] [Originally Added On: September 1st, 2011]
- Stem Cell Treatment for Autism: Community Outreach Miami, Florida - May 2011 [Last Updated On: September 2nd, 2011] [Originally Added On: September 2nd, 2011]
- Rylea returns home after stem cell treatment in China [Last Updated On: September 3rd, 2011] [Originally Added On: September 3rd, 2011]
- Stem Cell Treatments and ALS - www.StemCellRegenMed.com [Last Updated On: September 4th, 2011] [Originally Added On: September 4th, 2011]
- Patient with ALS Receiving Stem Cell Treatment - www.StemCellRegenMed.com [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- Stem Cell Therapy Success [Last Updated On: September 6th, 2011] [Originally Added On: September 6th, 2011]
- Lisa Ray Opens Up About Her Stem Cell Treatment Experience [Last Updated On: September 17th, 2011] [Originally Added On: September 17th, 2011]
- Repair Your Joint Injuries With Stem Cell Therapy | Los Angeles | Beverly Hills | Hollywood [Last Updated On: September 18th, 2011] [Originally Added On: September 18th, 2011]
- What could stem cell therapy do for Peyton? [Last Updated On: September 21st, 2011] [Originally Added On: September 21st, 2011]
- Peyton Manning Stem Cell Therapy: Some Doctors Cry Foul Over European Treatment [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- Adickes: Stem cell therapy [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- Webinar 1, Stem cell therapy basics, what is available today? [Last Updated On: September 30th, 2011] [Originally Added On: September 30th, 2011]
- Stem Cell Treatment for Leukemia at UCH [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Testimonial 4 of Duchenne Muscular Dystrophy after Stem Cell Therapy [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- The Spinal Cord Journey - Stem cell therapy stories from three spinal cord injury patients [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Parkinson Stem Cell Treatment [Last Updated On: October 7th, 2011] [Originally Added On: October 7th, 2011]
- " Embryonic" and "Adult" Stem Cell Research explained by David Kupelian [Last Updated On: October 11th, 2011] [Originally Added On: October 11th, 2011]
- Stem Cell Treatment for Heart Failure [Last Updated On: October 12th, 2011] [Originally Added On: October 12th, 2011]
- Stem Cell Therapy for Sickle Cell Anemia - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- Stem Cell Therapy Skin Repair and Anti-Wrinkle Cream - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- Stem Cell Treatment for Multiple Sclerosis - Community Outreach, San Diego: David Oliver - Video [Last Updated On: October 15th, 2011] [Originally Added On: October 15th, 2011]
- Spinal Cord Injury Patient after Stem Cell Treatment - Juan Carlos Murillo - Video [Last Updated On: October 16th, 2011] [Originally Added On: October 16th, 2011]
- Macular degeneration - Stem Cell therapy (English subtitles) - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- stem cell research - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- Diabetes- Stem cell therapy (english) - Video [Last Updated On: October 19th, 2011] [Originally Added On: October 19th, 2011]
- First Spinal-Cord Surgery With Stem Cells - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- The Skin Gun - Video [Last Updated On: October 23rd, 2011] [Originally Added On: October 23rd, 2011]
- Heart Congestion Failure- stem cell therapy (english) - Video [Last Updated On: October 24th, 2011] [Originally Added On: October 24th, 2011]
- Improvement seen in Duchenne Muscular Dystrophy after Stem Cell Therapy - Video [Last Updated On: October 24th, 2011] [Originally Added On: October 24th, 2011]
- Joseph, Friedreich's Ataxia, before stem cell treatment at Tiantan Puhua Hospital Beijing - Video [Last Updated On: October 25th, 2011] [Originally Added On: October 25th, 2011]
- Ataxia - Stem Cell Treatment TV Special (Part 1) - Video [Last Updated On: October 25th, 2011] [Originally Added On: October 25th, 2011]
- COPD and Stem Cell Treatments - www.StemCellRegenMed.com - Video [Last Updated On: October 26th, 2011] [Originally Added On: October 26th, 2011]
- Rheumatoid Arthritis Stem Cell Treatment - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- Stem Cells Repair Joint Cartilage - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- Soon stem cell cure for hearing loss - Video [Last Updated On: October 27th, 2011] [Originally Added On: October 27th, 2011]
- Extra: The Promise of Stem Cell Treatment - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - A Father's Story - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Stem cell treatment by Adiva Health Care India after Spinal Cord Injury - Video [Last Updated On: October 29th, 2011] [Originally Added On: October 29th, 2011]
- Macular Degeneration: Spotlight on Stem Cell Research - Mark Humayun - Video [Last Updated On: October 29th, 2011] [Originally Added On: October 29th, 2011]
- Stem Cells to Treat Acne Scarring | Los Angeles | Hollywood | Beverly Hills - Video [Last Updated On: October 30th, 2011] [Originally Added On: October 30th, 2011]
- Stem Cell Treatment Kidney Failure - Video [Last Updated On: November 5th, 2011] [Originally Added On: November 5th, 2011]
- Stem Cell Miracle From Cord Blood - Video [Last Updated On: November 7th, 2011] [Originally Added On: November 7th, 2011]
- Stem Cell Therapy: Psoriatic Arthritis Treatment - Video [Last Updated On: November 8th, 2011] [Originally Added On: November 8th, 2011]
- Deafness: Spotlight on Stem Cell Research - Karen Doyle - Video [Last Updated On: November 9th, 2011] [Originally Added On: November 9th, 2011]
- Daniel Deeter Testimonial for Fetal Stem Cell Treatment at Kyiv, Ukraine - Video [Last Updated On: November 12th, 2011] [Originally Added On: November 12th, 2011]
- Stem Cell Treatment Fibromyalgia - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- Stem Cell Treatment Kidney Disease - Video [Last Updated On: November 14th, 2011] [Originally Added On: November 14th, 2011]
- Heart patient sees results in stem cell study - Video [Last Updated On: November 15th, 2011] [Originally Added On: November 15th, 2011]
- Heart health: Patient's own stem cells repaired damage - Video [Last Updated On: November 15th, 2011] [Originally Added On: November 15th, 2011]
- StemCellTV Daily Report-November 15, 2011 - Video [Last Updated On: November 16th, 2011] [Originally Added On: November 16th, 2011]