Corporate Banner
Satellite Banner
Genomics
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 New Data from ZFP Therapeutic® Program in Hemophilia B
Studies expand potential of ZFN-mediated genome editing as a therapeutic modality.
Wednesday, December 14, 2011
Genetically Modified Stem Cells may Have Therapeutic Application to X-SCID
A study demonstrating therapeutic utilization of human stem cells, including application to X-SCID was presented at the 10th ASGT meeting.
Monday, June 04, 2007
Scientific News
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Growing Hepatitis C in the Lab
Recent discovery allows study of naturally occurring forms of hepatitis C virus (HCV) in the lab.
Inciting an Immune Attack on Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
Reprogramming Cancer Cells
Researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Surprising Mechanism Behind Antibiotic-Resistant Bacteria Uncovered
Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.
How DNA ‘Proofreader’ Proteins Pick and Edit Their Reading Material
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have discovered how two important proofreader proteins know where to look for errors during DNA replication and how they work together to signal the body’s repair mechanism.
Fat in the Family?
Study could lead to therapeutics that boost metabolism.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
Skyscraper Banner

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!