Two Baylor College of Medicine researchers have received Translational Research Grants from the Leukemia and Lymphoma Society for projects that use immunotherapy approaches to treat leukemia.

Dr. Stephen Gottschalk, professor of pediatrics and in the Center for Cell and Gene Therapy at Baylor, Texas Children’s Hospital and Houston Methodist Hospital, and Dr. Caroline Arber, assistant professor in the Department of Medicine and in the Center for Cell and Gene Therapy, both received three-year, $600,000 grants through the Society’s Translational Research Program, which funds new and innovative research that shows high promise for translating basic biomedical knowledge to clinical application. 

Gottschalk’s project focuses on developing an effective immunotherapy for acute myeloid leukemia (AML). 

“AML is a type of blood cancer that is in need of new therapies, as patients suffering from high-risk disease have little chance of cure,” said Gottschalk. “Cancer treatments consisting of the infusion of T cells – a component of the patient’s own immune system – that recognize parts of tumors have shown promise in early clinical studies.” 

He and his research colleagues have developed a new strategy to produce AML-specific T cells with a genetic approach that redirects not only genetically modified cells, but also unmodified T cells to AML cells. Studies in his laboratory have shown good activity of the AML-specific T cells against leukemia in preclinical models that closely mimic human disease.

“In this grant we are now planning to build on our encouraging results. We are proposing to include a ‘safety switch’ into our AML-specific T cells for use in humans, develop clinical grade reagents and obtain all regulatory approvals to conduct a clinical study. At the end of the grant we expect to have everything in place to conduct a clinical study to test the anti-leukemia activity of our T cells in patients with AML.” 

Arber’s research will address problems that can occur after hematopoietic stem cell transplantation, a common treatment for leukemia, lymphoma and myeloma patients. 

“Transplantation of blood-forming stem cells from a healthy person to a patient with blood cancer, such as leukemia, can cure these diseases,” she said. “However, the patient’s immune system is significantly weakened by this procedure, which frequently leads to serious or fatal viral infections, and unfortunately, the blood cancer can also come back. We propose a single approach that can overcome both problems.”

She and her research group have previously shown that T cells from healthy people manipulated in the lab can be used to treat infections and blood cancer in patients by training the cells to recognize viruses that cause infections as well as the blood cancer cells themselves. The modified T cells are given to the patient, where they can protect against viral infections and attack cancer cells. For the T cells to completely destroy the cancer, however, they need to be able to survive in the body for a long time. 

“In this project, we will test new ways of ensuring these cells live longer in the patients by making them recognize viruses and cancer cells at the same time, and ‘trick’ them into thinking the cancer cell is a type of virus infection. We will also engineer the cells to enable faster growth in the presence of a chemical that we know is produced in the same locations that the cancers grow. We think that this three-fold approach will protect patients from viral infections, improve the persistence and anti-cancer actions of the T cells and eradicate the cancer,” she said.

Gottschalk is also with Texas Children’s Cancer Center, a joint program of Baylor and Texas Children’s Hospital and the pediatric program of Baylor’s Dan L Duncan Cancer Center.