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Sangamo BioSciences and City of Hope Announce License Agreement and Research Collaboration to Develop Treatment for Brain Cancer


Posted on: 12/14/2006

Press Release Source: Sangamo BioSciences, Inc.

Sangamo BioSciences and City of Hope Announce License Agreement and Research Collaboration to Develop Treatment for Brain Cancer
Tuesday December 12, 7:00 am ET
 
Data Presented at the 48th Annual Meeting of the American Society of Hematology

 

DUARTE, Calif. and RICHMOND, Calif., Dec. 12 /PRNewswire-FirstCall/ -- City of Hope (COH), a leading California biomedical research facility and Comprehensive Cancer Center, and Sangamo BioSciences, Inc. (Nasdaq: SGMO - News) today announced that Sangamo has entered into an exclusive, worldwide license agreement with COH for intellectual property related to a chimeric immunoreceptor useful in treating human cancers. Sangamo and COH have also entered into a research collaboration to develop a novel cell therapy combining this technology with Sangamo's proprietary zinc finger DNA-binding protein nuclease (ZFN(TM)) technology for treatment of glioblastoma multiforme (GM), a progressive and usually fatal brain cancer.

Sangamo scientists are collaborating with Michael C.V. Jensen, M.D., Associate Chair, Division of Cancer Immunotherapeutics and Tumor Immunology, City of Hope, who has developed novel chimeric immunoreceptors called zetakines that can be engineered into human immune cells to generate a population of cells that can specifically recognize and destroy cancer cells. Dr. Jensen is already using these engineered cells in clinical trials for malignant gliomas and lymphoma. The aim of the current collaboration is to use Sangamo's ZFN gene modification technology to enable deletion of the glucocorticoid receptor (GR), a gene that limits the benefit of this novel therapy. Glucocorticoids are steroids that are widely used in glioma patients. The specific deletion of GR in the zetakine, anti-glioma T-cells will allow this novel immune therapy to be used in the presence of glucocorticoids.

"We are excited to be collaborating with Dr. Jensen and City of Hope to develop a treatment for this aggressive and malignant disease," said Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "Dr. Jensen has generated compelling data in animal models and has already successfully treated patients with his zetakine-modified T- cells in an ongoing clinical trial. However, he is currently unable to use this approach in patients who are receiving glucocorticoids to control swelling of the brain that is often a consequence of the disease, the related surgery, and its treatment. In addition, this approach is currently patient specific -- which makes it time and labor-intensive. We believe that our ZFN technology may provide a solution to this problem and enable us to develop an 'off the shelf' cell product that can be used in all GM patients. Our collaboration is going well and the early data related to the work have been presented this week at the annual meeting of the American Society of Hematology (ASH)."

Dr. Jensen has developed an IL-13 zetakine that, when expressed in cytotoxic or "killer" T-cells, enables them to seek out and destroy glioblastoma cells in the brain. In his current clinical protocol, T-cells are removed from a patient with GM and modified to express the zetakine. These modified cells are infused into the brain following surgery for the targeted elimination of residual tumor cells. Frequently, however, glucocorticoids must be administered to patients post-surgery to stop the brain from swelling. Glucocorticoids inactivate or kill the desirable T-cells through a protein on the T-cell surface known as the glucocorticoid receptor (GR). Cells without a functional GR are drug-resistant and are therefore available to destroy tumor cells. Dr. Jensen and his colleagues are collaborating with Sangamo scientists to generate zetakine positive, GR-negative T-cells.

"The combination of our two technologies holds tremendous promise for combating glioblastoma and other life threatening cancers," said Dr. Jensen. "This is an exciting opportunity to apply a novel technology for gene modification to T cell immunotherapy of brain cancers to create a cell product which can be used in combination with glucocorticoids to treat patients with GM."

Sangamo scientists have engineered ZFNs specifically targeted to the glucocorticoid receptor gene. Data were presented yesterday at the ASH annual meeting held in Orlando, Florida, that demonstrate that these ZFNs cleave their intended target sequences with high specificity and efficiency resulting in the knockout of GR and the creation of glucocorticoid resistant cells. Moreover, they demonstrated that these ZFNs can stimulate the integration of an IL-13 zetakine-encoding DNA molecule directly into the site of the GR gene. Thus, this procedure results in the simultaneous knockout of GR and addition of the IL-13 zetakine in a genetically defined manner. These data support the notion that ZFN-modified cells can be engineered to express chimeric antigen receptors from a predetermined genomic locus and may provide a general approach to generating effective cellular immunotherapies.

"We are excited about this approach and are committed to moving this program into the clinic as soon as possible," said Edward Lanphier, Sangamo's president and CEO. "We are very pleased to be working with COH and Mike Jensen and his team who have developed this novel approach to the treatment of GM. We believe that, in combination with our proprietary ZFN technology, we have the opportunity to broaden the patient population that could benefit from these advances."

Under the terms of the license agreement, Sangamo will pay COH an up-front license fee and annual maintenance fees. COH is also eligible for payments relating to clinical milestones, royalties and a portion of any revenue that Sangamo may realize from sublicensing agreements. The license granted to Sangamo is exclusive for the treatment or prevention of disease in humans using a combination of the zetakine and disruption of the expression or function of an endogenous gene.

"We are pleased to enter into these agreements with Sangamo. This is another example of how City of Hope's unique mix of innovative technology, translational infrastructure and our ability to forge partnerships with companies can help advance the frontiers of medical science," said Larry A Couture, Ph.D., Senior Vice President and Founding Director, Center for Applied Technology Development, City of Hope. "Sangamo has a powerful technology that may provide an elegant solution to the issues that Dr. Jensen has encountered. One of City of Hope's important missions is to translate scientific developments from the bench to the patient as efficiently as possible. We look forward to working collaboratively to accomplish this."

About Gliomas

Gliomas are the most common type of primary brain tumors; 20,000 cases are diagnosed and 14,000 glioma-related deaths occur annually in the United States. Glioblastoma multiforme, a type of glioma, is rapidly progressive and nearly uniformly lethal. Currently, malignant glioma is managed through surgery and radiation that often exacerbates the already severe symptoms caused by the location of the tumor. With modern surgical and radiotherapeutic techniques the mean duration of survival has increased to 82 weeks, although 5-year survival rates have only increased from 3 to 6%. Resections of >90% of bulky tumors are usually attempted provided that vital functional anatomy is spared. The addition of chemotherapy to resection and radiation provides only marginal survival advantage to patients. Approximately 80% of recurrent tumors arise from remnants of the original incompletely resected tumor. The median survival of recurrent glioblastoma multiforme patients treated with re- resection is 36 weeks.

About Sangamo BioSciences, Inc.

Sangamo BioSciences, Inc. is focused on the research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic(TM) development program is currently in a Phase 2 clinical trial for evaluation of safety in patients with diabetic neuropathy. Phase 1 clinical trials are on-going to evaluate a ZFP Therapeutic for peripheral artery disease. Other therapeutic development programs are focused on ischemic heart disease, neuropathic pain, cancer and infectious and monogenic diseases. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA- binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TF(TM)) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFN(TM)) for therapeutic gene modification as a treatment for a variety of monogenic diseases, such as X- linked SCID and hemophilia, and for infectious diseases, such as HIV. Sangamo has established several Enabling Technology Agreements with companies to apply its ZFP Technology to enhance the production of protein pharmaceuticals. For more information about Sangamo, visit the company's web site at www.sangamo.com.

About City of Hope

City of Hope is a leading research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a Comprehensive Cancer Center, the highest honor bestowed by the National Cancer Institute, and a founding member of the National Comprehensive Cancer Network, City of Hope's research and treatment protocols impact care throughout the nation. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics and shares its scientific knowledge with medical centers locally and globally, helping patients battling serious diseases. For more information, visit www.cityofhope.org.

This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references to the development of a novel cell therapy for the treatment of glioblastoma multiforme, research and development of other novel ZFP TFs and ZFNs, clinical trials and therapeutic applications of Sangamo's ZFP technology platform. Actual results may differ materially from these forward-looking statements due to a number of factors, including technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. See the company's SEC filings, and in particular, the risk factors described in the company's Annual Report on Form 10-K and its most recent 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

 



Source: Sangamo BioSciences, Inc.


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