Drs. Nabil Ahmed, Stephen Gottschalk and Jason Yustein of Baylor College of Medicine and Texas Children’s Cancer Center have received a total of $600,000 in grants from Alex’s Lemonade Stand Foundation to support their work to find innovative new treatments for childhood cancer.

Ahmed, assistant professor of pediatrics - oncology at BCM, and Gottschalk, professor of pediatrics - oncology at BCM, each received an Innovation Award from the foundation. The $250,000 grants provide critical seed funding for experienced investigators using novel approaches to find causes and cures for childhood cancers.

Immunotherapy approach

The Innovation Award will support Ahmed’s work to develop an immunotherapy approach to treat high-grade glioma, or HGG, a brain tumor that is virtually incurable. Immunotherapy is the study and development of treatments that use the body’s own immune system against disease.

Ahmed and his research team will generate a universal cancer-fighting T-cell from glioma patients that can target multiple antigens expressed on the HGG cell surface but not on normal brain tissue. They hope that by targeting multiple antigens, it will offset a phenomenon called "antigen escape" that results from targeting a single antigen. Discovered in Ahmed’s lab, this phenomenon refers to the ability of specific antigens to escape targeted therapy by eliminating the specific molecule the immune cells target.

"Knowledge gained from this project will be used to justify and develop a clinical trial to treat patients with HGG," said Ahmed. "In addition, this research could well have applicability for immunotherapy to other brain tumors and could conceptually impact other cancers outside the central nervous system."

Gottschalk’s Innovation Award also will support his research on cancer treatments using immunotherapy. While this is a promising treatment approach, Gottschalk said the body’s immune defenses against cancers often fail because the cancers do not induce or actively inhibit immunity.

Counteract limitation

His research team has developed a new approach to counteract this limitation by engineering T cells to secrete "Engagers" that recognize structures on cancer cells and T cells themselves. These Engagers redirect engineered and "bystander" T cells to kill cancer cells.

"We will generate Engager T cells for two pediatric malignancies, which are difficult to cure with current approaches, including recurrent leukemia and neuroblastoma. The antitumor activity of Engager T cells will be tested in preclinical models that closely mimic human disease," said Gottschalk.

Ahmed and Gottschalk are both part of the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and the Methodist Hospital.

Metastatic osteosarcoma

Dr. Jason Yustein, assistant professor of pediatrics - oncology at BCM, received the Young Investigator Award from Alex’s Lemonade Stand. This $100,000 grant is designated for new researchers and physicians to pursue promising research.

The grant will support Yustein’s research on metastatic osteosarcoma. This is a very aggressive type of bone cancer with a poor outcome, Yustein said.

Yustein and his research collaborators have analyzed genes and determined pathways that are abnormally functioning, including the identification of key alterations in the Wnt signaling pathway in metastatic tumors. Through the use of a novel mouse model of metastatic osteosarcoma, they identified diminished expression of genes that act as critical inhibitors of this pathway in the metastatic tumors.

"When placed back into human metastatic osteosarcoma cells, we proved that these genes biologically contribute toward controlling the development of metastatic disease. We propose to further investigate the importance of this pathway and its role in metastatic progression. In addition, we intend to test novel drugs that target the Wnt signaling pathway using our mouse model that spontaneously develops metastatic osteosarcoma," Yustein said

These grants are part of more than $7 million in new medical research grants awarded by Alex’s Lemonade Stand Foundation in 2013. The foundation is dedicated to finding cures for all kids with cancer by support research into new treatments and cures.

Texas Children’s Cancer Center is a joint program of Baylor College of Medicine and Texas Children’s Hospital.