My cycling class instructor at the local gym is a family friend and oncology nurse, who works and recently got promoted to a management position at the City of Hope (located in the San Gabriel Valley of Los Angeles County), which is a private, not-for-profit clinical research center, hospital and graduate medical school, dedicated to the prevention, treatment and cure of cancer and other life-threatening diseases including diabetes and HIV/AIDS.
After reading lots of recent posts here with keen interest in CAR-T research and therapy, this weekend after class, I asked her, what was happening at the City of Hope, specifically, regarding CAR-T research and therapy for solid tumors. I related to her that my cursory search found that CAR-T had so far been tested on hundreds of patients, mostly with blood cancers and that solid tumors posed more of a challenge. She told me that City of Hope researchers recently were the first to achieve remission using CAR-T cell therapy for aggressive brain tumors, specifically, the deadly glioblastoma. She told me to go to the City of Hope website for details.
Here’s what I found with my emphasis in bold:
City of Hope Researchers Achieve Remission Using CAR-T Cell Therapy for Aggressive Brain Tumors, December 28, 2016
https://www.cityofhope.org/nejm-car-t-case-study
DUARTE, Calif. — 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 IL13Ra2 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, IL13Ra2, 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.”
Here’s a must see video about the City of Hope treatment of the patient (a surgeon at Seattle Children’s Hospital) with 5 brain tumors and a tumor in his spine.
https://www.cityofhope.org/car-t-cell-therapy-effective-for-…
I found the following at the New England Journal of Medicine website that provides more details (need a subscription for the full report):
http://www.nejm.org/toc/nejm/375/26
Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy
A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Ra2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes — infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Ra2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362.)
The website reveals the supporting grants:
Supported by grants from Gateway for Cancer Research, the Food and Drug Administration, the California Institute for Regenerative Medicine, the CIRM Alpha Stem Cell Clinics Network, and the National Cancer Institute (NCI) and National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH.
http://www.nejm.org/doi/full/10.1056/NEJMoa1610497
Here’s a KITE video, discussing the future of CAR-T therapies and relating a mindset on solid tumors, according to Adrian Bot MD, PhD, Vice President, Scientific Affairs, Kite Pharma.
https://www.youtube.com/watch?v=ikJ1UyYfnK0
Lots of major achievements and accomplishmentS to date, but there’s still a lot of challenges ahead to overcome.
Regards,
Ray
