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CAR-T Cells Successfully Treats Glioblastoma Patient. Is This a Game Changer?

DECEMBER 29, 2016
James Radke, PhD
This week in the New England Journal of Medicine, clinicians at City of Hope report on a glioblastoma patient being successfully treated with his own genetically modified CAR-T cells. 
 
The patient was a 50-year-old male with recurrent multifocal glioblastoma who had already undergone standard of care therapy of resection, radiation and temozolomide. The tumors involved both the brain and the spinal cord.
 
The patient received CAR-T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2) that was administered in multiple infusions over 220 days through 2 intracranial delivery routes — infusions into the resected tumor cavity followed by infusions into the ventricular system.
 
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. 

Game Changer

In a press release, lead investigator, Behnam Badie, MD, chief of neurosurgery at City of Hope said:
 
“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.”
 
Dr Badie added that this treatment has great promise and could be a ’game changer' for how brain cancers are treated.

Dr Badie said:

“I believe these recent results show we have a potential breakthrough treatment that may have a remarkable impact on patients with malignant brain tumors.”
 
Christine Brown, PhD, Heritage Provider Network Professor in Immunotherapy and associate director of the T Cell Therapeutics Research Laboratory at City of Hope added:
 
 “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.”

Trial Underway

The therapy, known as MB-101, is currently being developed by Mustang Bio, a susidiary of Fortess Biotech. A phase 1 study is currently being conducted at City of Hope to assess MB-101 in patients with recurrent and refractory malignant glioblastoma.

For more information, visit clinicaltrials.gov

About CAR-T Cells

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 and grow a reservoir of cancer-killing cells that can attack and destroy future glioma tumor cells.

For more information, visit www.mustangbio.com

About Glioblastoma

Glioblastoma multiforme is a rare but very aggressive form of cancer. Glioblastomas can be classified as primary or secondary. Primary glioblastoma tends to occur in older adults (> 50 years) and appear quite suddenly (less than 3 months from initial symptoms to diagnosis). Secondary glioblastoma is less common and occurs in younger patients (< 45 y). These tumors can be present for years before symptoms appear.
 
Genetic studies are showing several mutations present in the patients with glioblastomas. For example, Loss of heterozygosity (LOH) on chromosome arm 10q is the most frequent gene alteration for both primary and secondary glioblastomas and occurs in 60-90% of cases. This mutation appears to be specific for glioblastoma multiforme and is found rarely in other tumor grades. This mutation is associated with poor survival. Other mutations associated with some glioblastomas include: mutations in p53; epidermal growth factor receptor (EGFR) gene; amplification or overexpression of MDM2 amplification or overexpression of PDGFR; PTEN mutations. Numerous other mutations have also been identified.

Standard therapy for glioblastoma consists of surgical resection, radiation therapy, and chemotherapy. Patients treated with this standard therapy tend to survive for approximately 12 months. Without treatment, survival is about 3 months. The most common chemotherapy used is the orphan drug temozolomide (Temodar). Other agents given orphan drug status to treat patients with glioblastoma include bevacizumab (Avastin) and polifeprosan 20 with carmustine (Gliadel). As more information becomes available on the genetic heterogeneity of glioblastomas, it is hopeful that a more effective treatment will be found.

Reference

Brown CE, Alizadeh D, Starr R, et al. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. New Engl J Med. 2016;375:2561-2569. DOI: 10.1DOI: 10.1056/NEJMoa1610497056/NEJMoa1610497
 
 


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