Corporate Banner
Satellite Banner
Pharma Outsourcing
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Sangamo and City of Hope Granted Strategic Partnership Award from CIRM

Published: Saturday, May 31, 2014
Last Updated: Saturday, May 31, 2014
Bookmark and Share
First clinical application of genome editing technology in hematopoietic stem/progenitor cells.

Sangamo BioSciences, Inc. has announced that the California Institute for Regenerative Medicine (CIRM) has granted a $5.6 million Strategic Partnership Award to fund clinical studies at City of Hope to develop a potentially curative ZFP Therapeutic for HIV/AIDS based on the application of Sangamo's zinc finger nuclease (ZFN) genome-editing technology in hematopoietic stem/progenitor cells (HSPCs).

"Sangamo's powerful and precise ZFN-mediated genome editing technology allows us to modify a patient's own stem cells and perform 'autologous' transplants, with the potential to replicate the functional cure obtained for the 'Berlin Patient' in any HIV-infected individual," said John A. Zaia, M.D., Professor & Chair, Department of Virology, Beckman Research Institute of City of Hope and a member of the clinical team that will be conducting the pilot clinical trial of this ZFP Therapeutic. "We are very pleased to be working with Sangamo to test this important immunologic approach in the clinic."

The four-year grant provides matching funds to support evaluation of Sangamo's stem cell-based ZFP Therapeutic in HIV-infected individuals in a clinical trial conducted at City of Hope. The grant application entitled, "A Phase 1, Open-Label Study to Assess the Safety, Feasibility and Engraftment of Zinc Finger Nucleases (ZFN) CCR5-Modified Autologous CD34+ Hematopoietic Stem/Progenitor Cells (SB-728mR-HSPC) with Escalating Doses of Busulfan in HIV-1 (R5) Infected Subjects with Suboptimal CD4 Levels on cART" tied for the highest scientific score and was one of two applications recommended for funding in this round of CIRM's Strategic Partnership Awards.

CCR5 encodes a critical co-receptor for HIV infection of immune cells. A naturally occurring mutation of the CCR5 gene, CCR5 delta-32, results in the loss of expression of the CCR5 protein on the surface of immune cells. Individuals who carry the CCR5 delta-32 mutation on both copies of their CCR5 gene (CCR5 delta-32 homozygotes) are not susceptible to the most common strain of HIV.

One HIV-infected individual, known as the 'Berlin Patient,' underwent stem cell transplantation with HSPCs from a CCR5 delta-32 homozygote achieving what is considered to be a "functional cure" of his HIV and enabling him to remain off antiretroviral medication for more than six years. As stem cell transplantation is limited by the availability of HLA-matched, homozygous CCR5 delta-32 donors, Sangamo's approach is designed to make HIV-infected individuals their own donor using ZFN technology to disrupt the CCR5 gene in their HSPCs.

Sangamo's ZFN-mediated genome-editing technology has already been successfully applied to the generation of CCR5-modified autologous CD4 T-cells (SB-728-T), a program which is currently in a Phase 2 clinical trial in HIV-1 infected subjects. A number of clinical studies, in more than 70 subjects, have demonstrated that SB-728-T treatment is generally safe and well-tolerated. Of importance to the HSPC approach, the ZFN-modified CCR5-edited T-cells engraft, persist over time, and traffic throughout the body, including sites such as the gut-associated lymphoid tissue, that house the viral reservoir.

The reservoir is a "store" of the virus that cannot be diminished by treatment with antiretroviral medications. In contrast, clinical data support the erosion of this reservoir in SB-728-T-treated subjects over time. Immunologic analyses have also provided insight into baseline immunologic parameters that are required for the successful engraftment of SB-728-T, and include the inflammatory status of the HIV-infected individual.

Treatment for HIV-1 infection with ART results in diminished HIV-1 replication and increased CD4 cell counts. However, CD4 cell counts fail to recover in approximately 20% HIV-1 infected patients, despite optimal treatment and completely suppressed viral replication and these individuals, known as immunologic non-responders (INR), are at significant risk from progressive AIDS-related syndromes.

The suboptimal immune reconstitution in INR patients is thought to be influenced by several factors, including previous therapeutic failure, duration of anti-retroviral therapy, low CD4 counts at the initiation of ART, and persistent chronic immune activation, or inflammation, which makes them poor candidates for good SB-728-T engraftment. SB-728mR-HSPC is being developed as a new therapeutic strategy for this INR population.

The primary objective of the Phase 1, open-label study is to evaluate the safety and tolerability of the infusion of autologous ZFN-genome-edited, CCR5-disrupted HSPCs (SB-728mR-HSPC) in HIV-1 infected subjects who are on ART, have no detectable virus in the circulation, but have sub-optimal CD4 T-cell levels. Secondary objectives of the trial are to assess the engraftment and biologic activity of the infused CCR5 modified HSPCs cells that may help to define primary efficacy endpoints for future studies. These secondary objectives include engraftment, persistence and trafficking of the CCR5-disrupted HSPCs, effect of these cells on plasma viral loads during treatment interruption from ART and longitudinal changes in the viral reservoir.

"This is the first of several clinical applications of ZFN-based technology in stem cells," said Edward Lanphier, Sangamo's president and chief executive offices. "Results of this research can be expected to have a wide effect on the field, enhancing the impact of CIRM-funded research in multiple disease areas and applications, including our beta-thalassemia and sickle cell disease programs which are currently in preclinical development."

"CIRM continues to provide valuable support for innovative stem cell-based therapeutics," continued Mr. Lanphier. "This new award builds upon previous Disease Team funding by CIRM for pre-clinical development of our novel stem cell gene-therapy approach to HIV; we look forward to continuing our collaboration with City of Hope and CIRM as we bring this therapeutic to the clinic."

"These programs help bring together the most rigorous scientific research with companies that know how to do clinical trials and move therapies through the regulatory process," said Jonathan Thomas, Ph.D., J.D., Chairman of the stem cell agency's governing Board. "It's a partnership with a simple goal, get the most promising therapies to patients as quickly as possible."


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Sangamo BioSciences Announces Presentation of Preliminary Data From Phase 2 Study of SB-509
Early data demonstrates improvement in muscle function with SB-509 treatment compared to historic controls.
Thursday, December 10, 2009
Scientific News
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
NIH Launches Human RSV Study
Study aims to understand infection in healthy adults to aid development of RSV medicines, vaccines.
Computerized Flexible Needles Prove Themselves in Biological Tissue
The advantage of the system is that you can avoid obstacles with the needles or critical tissues and that the system during the insertion of the needle in real time can adjust the path if, for example, the tissue deforms.
DARWIN 2 24-week Monotherapy Data in RA Confirm Previous Results
Safety profile in DARWIN 2 consistent with previous filgotinib RA studies.
Researchers Publish Landmark “Basket Study”
Researchers from Memorial Sloan Kettering Cancer Center (MSK) have announced results from the first published basket study, a new form of clinical trial design that explores responses to drugs based on the specific mutations in patients’ tumors rather than where their cancer originated.
Agricultural Intervention Improves HIV Outcomes
A multifaceted farming intervention can reduce food insecurity while improving HIV outcomes in patients in Kenya, according to a randomized, controlled trial led by researchers at UC San Francisco.
Overdose of Vitamin D in Teenagers May Lead to Increased Cholesterol Levels
Dosing obese teens with vitamin D shows no benefits for their heart health or diabetes risk, and could have the unintended consequences of increasing cholesterol and fat-storing triglycerides. These are the latest findings in a series of Mayo Clinic studies in childhood obesity.
Phase 2 Trials Underway for New Single Dose Malaria Treatment
The new drug, which prevents the malaria parasite from reproducing and spreading, is now undergoing Phase II clinical trials in humans.
Promising Drug for Parkinson's Disease
A drug which has already been in use for decades to treat liver disease could be an effective treatment to slow down progression of Parkinson’s disease, scientists from the University of Sheffield have discovered.
Benefits of Early Antiretroviral Therapy in HIV Infection
Scientists have explored the clinical importance of starting treatment early in individuals suffering with HIV.
Scroll Up
Scroll Down
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!