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Treatment with reengineered CAR-T cells improves quality of life for patient with recurrent glioblastoma


City of Hope researchers at Duarte, California ( U.S. ) have 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 IL13Ralpha2 antigen which is common in brain cancer. A

The case study published in the New England Journal of Medicine ( NEJM ) 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.

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, IL13Ralpha2, 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.

The results of this case study have demonstrated 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.

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.
This promising treatment also greatly improves quality of life by preserving patients’ neurological function and minimizing the toxic side effects of other treatments.

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.

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% of patients make it past the five-year mark. ( Xagena )

Source: City of Hope, 2016

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