Dr. Meenakshi Hegde, instructor of pediatrics – hematology/oncology at Baylor College of Medicine, was awarded the 28th Schweisguth Prize from the International Society of Pediatric Oncology for the best scientific paper written by a trainee.

Hegde received the honor for her paper, "Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in High Grade Glioma." Her completed research paper was recently published in Molecular Therapy.

Research presentation

She will deliver a presentation on her research at the 45th Congress of the International Society of Paediatric Oncology on Sept. 27 in Hong Kong.

"I feel honored and humbled to have received the prestigious Schweisguth prize and will take this wonderful opportunity with great gratitude to share our work with the fellow oncologists from around the world," Hegde said.

Her research focuses on developing novel treatment for malignant gliomas that targets more than one tumor associated-proteins simultaneously with the aim of decreasing the risk of tumor recurrence. Malignant gliomas are tumors that often do not respond to even the most aggressive forms of therapy currently available. Less than 25 percent of children with this type of brain tumor survive after five years.

Though early clinical trials using immune cells called T cells targeting a specific protein on the tumor cell surface to treat cancer has shown promising results, outcome has not been optimal in malignant gliomas mainly because of their heterogenous nature – meaning the expression of proteins is variable from tumor to tumor and within a single tumor.

"Using T cells specific for a single protein can result in selective survival of those tumor cells that do not express the protein. This leads to tumor recurrence after therapy," Hegde explained.

Expression pattern

Hegde and her research colleagues studied the expression pattern of three different glioma-associated proteins – HER2, IL-13Rα2 and EphA2 – in many different patients. Using this data, they successfully generated modified T cells from malignant glioma patients that can simultaneously target HER2 and IL-13Rα2, the combination that was most frequent in their patient group. They studied the function of these bispecific T cells in the lab and in animal models of human malignant glioma.

"Our results so far show that bispecific T cells simultaneously targeting two glioma associated-proteins improve tumor control and confer significant survival advantage to the treated animals in comparison to targeting a single protein only," Hegde said. "Our goal is to use the knowledge gained from this work to justify and develop a clinical trial with the hope of fulfilling the dire need for less toxic and more effective therapy for children with malignant glioma."

Hegde completed the research while working under the mentorship of Dr. Nabil Ahmed in in the brain tumor research program at Texas Children’s Cancer Center and at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist.