Multi-Center Pediatric Research Study Targets Cancer with T CellsNov 15, 2019
Researchers at the Children’s Hospital of Michigan, part of the Detroit Medical Center (DMC), the Wayne State University School of Medicine and the Barbara Ann Karmanos Cancer Institute in Detroit are partnering with Memorial Sloan Kettering Cancer Center in New York to offer patients a new investigational treatment option recently approved by the Food and Drug Administration (FDA) for children with neuroblastoma and osteosarcoma.
Believed to be the first of its kind, this pediatric therapy was developed by researchers Maxim Yankelevich, M.D., oncologist on staff at the Children’s Hospital of Michigan and assistant professor of pediatrics for the Wayne State University School of Medicine; Lawrence G. Lum, M.D., DSc., scientific director of immunotherapy and bone marrow transplant for the Karmanos Cancer Institute and professor of oncology medicine for the Wayne State University School of Medicine; Nai-Kong Cheung, M.D., Ph.D., head of the Neuroblastoma Program, and Enid A. Haupt, chair of Pediatric Oncology at Memorial Sloan Kettering; and Shakeel Modak, M.D., associate member at Memorial Sloan Kettering.
Neuroblastoma is the most common pediatric solid cancer, and osteosarcoma is the most common cancerous bone tumor in children and young adults. Despite significant improvements in treatment, the disease returns after chemotherapy in nearly four out of 10 newly diagnosed cases of high-risk neuroblastoma and osteosarcoma.
Recently, a new treatment called antibody immunotherapy made long-awaited improvements in the survival of high-risk neuroblastoma patients for the first time in almost 30 years. Despite advances with immunotherapy, the disease still recurs in a number of high-risk neuroblastoma patients even after treatment with monoclonal antibodies manufactured to specifically attack neuroblastoma.
Under the leadership of Dr. Lum and Dr. Yankelevich, with the support of Jeffrey Taub, M.D., FAAP, chief of oncology on staff at the Children’s Hospital of Michigan and professor of pediatrics for the Wayne State University School of Medicine, researchers have begun an investigational new treatment involving antibody therapy called Bispecific Antibody Armed T Cells (BATs). The therapy combines cell and antibody-targeted therapy to “clean up” remaining cancerous cells to prevent relapse after chemotherapy.
The new investigational research involves using the patient’s own immune T-Killer cells (a type of immune cell that fights cancer) by: 1) activating and expanding these T cells outside the body to produce billions of them; 2) targeting neuroblastoma and osteosarcoma by arming the T cells with the humanized bispecific antibody hu3F8 developed at Memorial Sloan Kettering Cancer Center. The antibody binds to GD2 protein (disialoganglioside expressed on tumors of neuroectodermal origin) on neuroblastoma/osteosarcomas and CD3 (cluster of differentiation 3) on T cells; and 3) introducing the BATs back into patients to destroy tumors and trigger immune responses against neuroblastoma and osteosarcoma tumors.
This approach has been tested successfully in other clinical settings, including treatment for metastatic breast cancer, by Dr. Lum, who is nationally and internationally known for pioneering the development of BATs, designing clinical trials and administering BATs to patients.
“The study using armed T cells for women with metastatic breast cancer showed an overall survival of 37 months, more than twice the overall survival in most clinical trials,” Dr. Lum said. “We have demonstrated successful treatment not only with breast cancer, but also with multiple myeloma, non-Hodgkin’s lymphoma and gastrointestinal cancers. It is especially encouraging that all of the patients treated, to date, have not experienced any dose-limiting side effects.”
The study aims to establish the safe dose of armed anti-GD2 T cells in children with neuroblastoma and osteosarcoma. Approximately 45 children at the Children’s Hospital of Michigan and Memorial Sloan Kettering will participate in the study.
"It feels great to take the next step in this study after years of laboratory research and preparations,” Dr. Yankelevich said. “It is important for young patients with high-risk pediatric cancers who fail standard treatments to have additional options like our study. A joint research and organizational effort of such institutions as Karmanos, Memorial Sloan Kettering and the Children’s Hospital of Michigan should enhance the chance of success."
Development of the study was made possible by donations from the Matthew Bittker Foundation. This phase of the study is supported by a $3.7 million R01 grant (R01 CA 182526) from the National Cancer Institute of the National Institutes of Health.