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  • CAR T cell therapy...

CAR T cell therapy promising treatment for recurrent pediatric brain cancer

Written By : Hina Zahid |Medically Reviewed By : Dr. Kamal Kant Kohli Published On 2020-05-03T18:00:34+05:30  |  Updated On 4 May 2020 11:23 AM IST
CAR T cell therapy promising treatment for recurrent pediatric brain cancer
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Two pediatric brain cancers that are challenging to treat if they recur, medulloblastoma and ependymoma, are the target of a clinical trial using a new type of therapy.Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation.

Researchers at Baylor College of Medicine, Texas Children's Hospital and the Hospital for Sick Children (SickKids) has developed a novel approach that delivers appropriately-targeted chimeric antigen receptor (CAR) T cell therapy directly into the cerebrospinal fluid that surrounds the tumor. The research has been published in the journal Nature Medicine.

The researchers report that this approach was effective in treating these cancers in mouse models of human disease. The findings support further clinical studies to evaluate this strategy to treat pediatric brain cancers, the most common cause of cancer death in childhood. Indeed, a first-in-child clinical trial currently is recruiting patients at Texas Children's Hospital and Baylor College of Medicine to test the safety and anti-tumor efficacy of this approach (Clinicaltrials.gov identifier: NCT02442297).

"Recurrences of medulloblastoma and ependymoma can be disseminated throughout the lining of the brain and spinal cord, which are bathed in cerebrospinal fluid. This location offers the opportunity to deliver therapies into the cerebrospinal fluid compartment and could provide a better chance for the therapy to reach and eliminate the tumor than administering it through the blood stream," said co-corresponding author Dr. Nabil Ahmed, associate professor of pediatrics and immunology, section of hematology-oncology at Baylor and Texas Children's Hospital.

"The vast majority of children with recurrent metastatic medulloblastoma or ependymoma currently have a deadly prognosis, so it is very exciting to think we have identified a novel approach to treat this underserved patient population," said co-corresponding author Dr. Michael Taylor, neurosurgeon, senior scientist in the Developmental and Stem Cell Biology program, Garron Family Chair in Cancer Research at SickKids, and professor in the Departments of Surgery and Laboratory Medicine and Pathobiology at the University of Toronto.

This project was led by Dr. Laura Donovan, post-doctoral fellow in the Developmental and Stem Cell Biology program at SickKids, who performed in-depth molecular studies of the target profile of recurrent medulloblastoma and ependymoma. These studied guided the design of CAR T cells engineered by Ahmed and colleagues at Baylor's Center for Cell and Gene Therapy and Texas Children's Hospital to target the most appropriate cancer molecules.

CAR T cells are a form of immunotherapy involving engineering of T cells, a type of immune cell that fights cancer. The researchers genetically engineered CAR T cells to recognize specific molecules on the surface of the tumor cells. When these CAR T cells encounter the tumor, they can fight it more effectively. CAR T cells have been impressively effective for patients with certain types of leukemia and are FDA-approved for this disease.

In mouse model studies, CAR T cells were administered into the cerebrospinal fluid around the tumor or into the blood stream of mice harboring multiple patient-derived medulloblastoma and ependymoma tumors. The tumor size and animal survival were studied for about 200 days.

The results showed that administering tumor-specific CAR T cells into the cerebrospinal fluid was more effective than administering them via the blood.

"As opposed to delivery through the blood, cerebrospinal fluid delivery overcomes the blood-brain barrier and also offers the advantage of minimizing exposure of other tissues of the body to the CAR T cells and, consequently, potential side effects," Donovan said.

In some of their experiments, the researchers combined CAR T cells with an approved cancer medication called azacytidine. The results showed that combining immunotherapy with azacytidine was significantly more effective than either treatment alone.

"This work was possible thanks to the concerted collaboration of our Pediatric Cancer Dream Team supported by Stand Up To Cancer® (SU2C) St. Baldrick's Foundation Translational Research Grant, which brought together scientists studying tumor genomics and tumor immunotherapy around the world to enable the design of more effective therapies for children with incurable and hard to treat cancers," Ahmed said.

For more details click on the link: http://dx.doi.org/10.1038/s41591-020-0827-2

pediatric brain cancermedulloblastomaependymomastem cell biologynature medicine
Source : Nature Medicine
Hina Zahid
Hina Zahid

    Hina Zahid Joined Medical Dialogue in 2017 with a passion to work as a Reporter. She coordinates with various national and international journals and association and covers all the stories related to Medical guidelines, Medical Journals, rare medical surgeries as well as all the updates in the medical field. Email: editorial@medicaldialogues.in. Contact no. 011-43720751

    Dr. Kamal Kant Kohli
    Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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