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First-of-its-kind Study of Peptide Vaccine by Pittsburgh Researchers Shows Evidence of Immunological Response in Children with Gliomas

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4/2/2012

In a first-of-its-kind study, researchers from Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh Cancer Institute (UPCI) Brain Tumor Program have demonstrated that peptide vaccines in children with gliomas, the most common type of brain tumor, not only were well-tolerated but also showed evidence of immunological responses. The results of the study will be presented during a press conference today at the AACR Annual Meeting 2012 in Chicago.

The study, led by Ian F. Pollack, M.D., F.A.C.S., F.A.A.P., chief, Pediatric Neurosurgery at Children’s Hospital’s Brain Care Institute and co-director of UPCI’s Brain Tumor Program, and Dr. Regina I. Jakacki, M.D., director of Pediatric Neuro-Oncology, enrolled 27 children with gliomas, including 16 with newly diagnosed brainstem gliomas, five with newly diagnosed cerebral high-grade gliomas and six with recurrent gliomas. Each child received serial doses of a peptide vaccine, which stimulates an immune response to a protein fragment present on their tumor cells.

“We’ve found that this vaccine is tolerated well with limited systemic toxicity, but we’ve also observed that there are some patients who have immunological responses in the vaccine target in the brain that can cause swelling and transient worsening and, subsequently, some of those children can have very favorable responses,” said Dr. Pollack, the Walter Dandy professor of neurological surgery and vice chairman for academic affairs in the department of neurological surgery at the University of Pittsburgh School of Medicine. “We’ve also demonstrated immunological responses in the majority of the kids.”

Children with eligible tumor types received a vaccine targeting glioma-associated antigen (GAA) proteins, including EphA2, IL13Rα2 and survivin, every three weeks, for a total of eight doses.

“These kids, who, for the most part, have intact and very strong immune systems, seem to mount an immune response against the vaccine very effectively at rates that may be even higher, I think, than have been noted in studies in adults,” Dr. Pollack said.

Among the 22 cases evaluated, three children had rapidly progressive disease, 15 had stable disease for more than three months, three had sustained partial responses, and one had prolonged disease-free status after surgery. An immune response analysis, which was completed in seven children, revealed responses in six children: to IL13Rα2 in five cases, EphA2 in three and survivin in three.

“This was the first study of its type that examined peptide vaccine therapy for children with brain tumors like this,” Pollack said. “The fact that we’ve seen tumor shrinkage in children with very high-risk tumors has been extremely encouraging and somewhat surprising.”

The study was funded by the National Institutes of Health and the Pediatric Low-Grade Glioma Initiative.

For more information about Dr. Pollack, Dr. Jakacki, or Children’s Hospital, visit www.chp.edu.

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