Immunotherapy slows childhood glioma

Immunotherapy with peptide vaccines may offer a much-needed therapeutic option for gliomas in children, which carry a poor prognosis despite current treatments.

In a pilot trial of subcutaneous vaccinations with peptides for glioma-associated antigen (GAA) epitopes in children who have been newly diagnosed with brain stem gliomas, cerebral high-grade gliomas, or recurrent gliomas, the immunotherapy was well tolerated and demonstrated immunologic and clinical activity, Dr. Ian F. Pollack reported April 2 at the annual meeting of the American Association for Cancer Research.

For the pilot study Dr. Pollack, chief of pediatric neurosurgery at Children’s Hospital of Pittsburgh Brain Care Institute, and his colleagues have enrolled 27 human leukocyte antigen (HLA) A2–positive children to date, including 16 who are newly diagnosed with brain stem gliomas, 5 with newly diagnosed high-grade gliomas, and 6 with recurrent gliomas. The GAAs were EphA2, interleukin-13 receptor alpha 2 (IL-13RA2), and survivin, he said.

All of the children received eight courses of subcutaneous vaccinations with peptides for GAA epitopes emulsified in Montanide-ISA-51 every 3 weeks, along with intramuscular injections of the immunoadjuvant poly-ICLC, which promotes the infiltration of effector T cells into intracranial gliomas.

“Our primary end points were safety and T-cell response against vaccine-targeted [GAAs],” he said, noting that treatment response was assessed clinically and by MRI.

The preliminary results reported at the meeting are based on an interim analysis of 22 evaluable patients. To date, no non–central nervous system toxicities have limited the vaccine dosages, Dr. Pollack said. Of the 22 children, 4 showed signs of rapidly progressive disease, 14 had stable disease for more than 3 months, 3 had sustained partial responses, and 1 had prolonged disease-free status after surgery, he reported.

Symptomatic “pseudoprogression” – consisting of transient neurologic deterioration and tumor enlargement, followed by tumor regression and stabilization on decreasing steroid doses with sustained partial response – was observed in four of the children with brain stem glioma, said Dr. Pollack, who is also codirector of the University of Pittsburgh Cancer Institute’s brain tumor program.

Results of the ELISPOT (enzyme-linked immunosorbent spot) assay, which was completed in seven of the children, showed responses in six of them. Specifically, the investigators observed responses to IL-13RA2 in five cases, EphA2 in three cases, and survivin in three cases, Dr. Pollack said.

“Based on what we’ve seen so far, it seems that these kids are able to mount immune responses to the vaccine at high rates, possibly higher than we’ve seen in adult studies,” likely because of their robust immune systems, he said in an interview.

The observation of immunologic and clinical response – particularly the evidence of tumor shrinkage in children with very high-risk tumors – “has been extremely encouraging and somewhat surprising,” Dr. Pollack reported. “This is the first study of its type that examined peptide vaccine therapy for children with brain tumors like this.”

The findings are especially notable because children with these tumors generally do not respond well to standard chemotherapy, he said, stressing that if further study validates the early findings, “immunotherapy may be a promising strategy to control tumor growth.”

The study was funded by the National Institutes of Health. Dr. Pollack disclosed having no potential conflicts of interest.

Source: Elsevier Medical News