Posted by: thepinetree on 12/28/2016 09:58 PM
Updated by: thepinetree on 12/28/2016 10:42 PM
Expires: 01/01/2021 12:00 AM
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City Of Hope Researchers Achieve Cancer Remission Using Car-T Cell Therapy On Glioblastoma Brain Tumors
Duarte, CA...City of Hope researchers recently reported on the successful treatment of a patient with recurrent multifocal glioblastoma using CAR-T therapy, a type of immunotherapy, to effectively attack cells with the IL13Rα2 antigen which is common in brain cancer. A case study published in the Dec. 29 edition of the New England Journal of Medicine outlined the results of a patient treated with his own genetically modified chimeric antigen receptor or CAR-T cells, using central memory T cells, a stem cell-like subset of immune cells.
The 50-year-old male reported in the case study presented with recurrent multifocal glioblastoma and was enrolled in the City of Hope phase I clinical trial after failing standard of care therapy of resection, radiation and temozolomide. The patient, however, failed to respond to the treatment and developed multifocal disease, with tumors involving both the brain and the spinal cord.
As part of the City of Hope clinical trial to test the safety of CAR-T cell therapy delivered directly to brain tumors, the patient received multiple infusions that were well tolerated. Regression was observed for both brain and spinal tumors, as well as increased numbers of immune cells in the cerebrospinal fluid, a clinical response that was sustained for 7.5 months after initiation of CAR-T cell therapy, according to the paper.
City of Hope is one of a few cancer centers in the United States offering studies in CAR-T cell therapy, and is the only cancer center investigating CAR-T cells targeting the high affinity IL-13 receptor, IL13Rα2, that is overexpressed in a majority of glioblastomas. City of Hope is also administering the therapy locally in the brain, by direct injection to the tumor site and/or through infusion in the ventricular system.
“By injecting the reengineered CAR-T cells directly into the tumor site and the ventricles, where the spinal fluid is made, the treatment could be delivered throughout the patient’s brain and also to the spinal cord where this particular patient had a large metastatic tumor,” said co-senior author of the New England Journal of Medicine publication, Behnam Badie, M.D., chief of neurosurgery at City of Hope.
“I believe these recent results show we have a potential breakthrough treatment that may have a remarkable impact on patients with malignant brain tumors.”
Badie said the results of this case study demonstrate that even at the lowest dosage, this type of therapy has tremendous promise and is a “game changer” in how brain tumors may be treated in the future.
“The most exciting thing about our study is that it proves a better treatment may be attainable,” said lead author and scientist Christine Brown, Ph.D., Heritage Provider Network Professor in Immunotherapy and associate director of the T Cell Therapeutics Research Laboratory at City of Hope. “We can take a patient who has actively growing advanced, metastatic multifocal glioblastoma, and we can see regression of all lesions, including in the spine. To date, that’s unheard of.”
Based on the early successful results seen in the phase I trial for intracranial CAR-T cell therapy, the researchers see enormous potential for a remarkable impact on a wide variety of patients. They remain encouraged that this promising treatment also greatly improves quality of life by preserving patients’ neurological function and minimizing the toxic side effects of other treatments.
City of Hope, with its clinical, research and production facilities all on one campus, is uniquely positioned to lead this work, Brown added. Few institutions are capable of harnessing the same comprehensive “bench to bedside” resources necessary for the discovery, development, manufacturing, quality assurance, testing and deployment of leading-edge treatments.
“City of Hope has accepted the challenge to try to make a therapy that can be used for patients with many different types of cancers,” said co-senior author Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of City of Hope’s T cell Immunotherapy Research Laboratory. “Our CAR-T program here is focused not only on leukemia, lymphoma and myeloma, but also on solid tumors including breast cancer, liver cancer and brain cancer, as a way to try to make effective immunotherapy options for difficult-to-treat cancers.”
Other collaborating authors include Darya Alizadeh, Ph.D., Renate Starr, M.S., Lihong Weng, M.D., Ph.D., Jamie R. Wagner, Araceli Naranjo, Julie R. Ostberg, Ph.D., M. Suzette Blanchard, Ph.D., Julie Kilpatrick, M.S.N., Jennifer Simpson, Anita Kurien, M.B.S., Saul J. Priceman, Ph.D., Xiuli Wang, M.D., Ph.D., Todd L. Harshbarger, M.D., Massimo D’Apuzzo, M.D., Julie A. Ressler, M.D., Michael E. Barish, Ph.D., Mike Chen, M.D., Ph.D., and Jana Portnow, M.D., all of City of Hope in Duarte, California; and Michael C. Jensen, M.D., of Seattle Children’s Hospital in Seattle, Washington.
The research is being funded through grants from the Gateway for Cancer Research Foundation, the Food and Drug Administration, the California Institute of Regenerative Medicine, and the National Cancer Institute and National Institute of Neurological Disorders and Stroke of the National Institutes of Health. Development of CAR-T cells are made in partnership with Mustang Bio, Inc., a Fortress Biotech Company and a clinical-stage biopharmaceutical company developing novel immunotherapies based on the research of Forman and Brown.
About CAR-T
The T cells are engineered by adding chimeric antigen receptors (CARs) that help the immune cells target tumors. Unlike other T cells, which attack and then die, memory cells remain in the patient's system for a longer period – possibly a decade or more – and grow a reservoir of cancer-killing cells that can attack and destroy future glioma tumor cells.
About Glioblastoma
Glioblastoma is a rare type of cancer that affects fewer than 200,000 people a year in the United States. It is among the deadliest of human cancers and comes with a devastating prognosis for patients since current treatment options often have poor outcomes. Median survival for glioblastoma is just over 14 months and only 3 percent of patients make it past the five-year mark.
About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 47 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution.
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