One Year Research Update:
Meenakshi Hegde, MD is a CureSearch Young Investigator conducting research at Baylor College of Medicine to determine if the body’s immune system, specifically T-cells, can be engineered to recognize and kill osteosarcoma cancer cells. Osteosarcoma is the most common bone cancer in children and adolescents under 20 and currently requires a combination of surgery and aggressive chemotherapy to treat. Survival rates of osteosarcoma are just 60-70%, and for those whose disease has spread or does not respond to conventional treatment, survival is much lower.
One year into her CureSearch-funded research, Dr. Hegde has designed and generated a novel “bispecific molecule” called ‘tanCAR’ or ‘tandem chimeric antigen receptor’ that when placed in T-cells, allows them to target two different cancer-specific proteins (HER2 and GD2) commonly seen on osteosarcoma cells. The HER2 and GD2 specific tanCAR consists of two portions, called ectodomain and endodomain. Ectodomain is the portion that projects on the T-cell surface and is responsible for recognizing and binding the specific proteins on the cancer cells. Following this, the endodomain, the portion that is inside the T-cell activates them. Activated T-cell in turn destroys the cancer cells that express the protiens while sparing the normal tissues.
In the second year of her CureSearch grant, Dr. Hegde will use different laboratory tests and then animal models to examine the functionality of the bispecific T cells. “I hope 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 osteosarcoma,” says Dr. Hegde.
Dr. Hegde’s work on HER2/GD2 specific tanCAR was chosen for the Young Investigator Award by the American Society of Pediatric Hematology-Oncology and she will be presenting the work at the ASPHO annual meeting in May, 2014.
Osteosarcoma is a primary bone cancer affecting approximately 400 children and adolescents in the United States each year. Current treatment for this cancer is usually extensive surgery followed by chemotherapy. Even with aggressive treatment, the survival rate is just 60-70%. Further, about 40% of patients with osteosarcoma experience metastatic (cancer that has spread) or recurrent disease. For these patients, the survival rates are even lower. New, more targeted approaches to treatment are needed to improve outcomes for patients with this cancer.
Recently awarded a Young Investigator grant by CureSearch for Children’s Cancer, Meenakshi Hegde, MD at Baylor College of Medicine is hoping her research on the body’s immune system, specifically T-cells, will lead to new treatment options. The job of the body’s immune system is to fight off disease, in this case, cancer. Thus, when an abnormal, or mutated, cell is created, the body should recognize it as different from the rest and eliminate it. When that doesn’t happen, diseases occur.
In osteosarcoma, the cancerous cells contain proteins that should not be present, causing the tumors to grow. Presence of these proteins varies from tumor to tumor and sometimes within a single tumor. Dr. Hegde hypothesizes that killing tumor cells using T-cells that recognize a single protein will result in the survival of tumor cells that do not express this protein leading to tumor recurrence after therapy. She plans to engineer T-cells, that are designed to target the two proteins most commonly expressed in osteosarcoma, with the goal of decreasing the risk of tumor recurrence.
Her work builds on a previously proven model in which a single molecule expressed on T-cell targets two different proteins and on a Phase I and Phase II clinical trial already underway. If successful, Dr. Hegde’s work will pave the way for the creation of new immunotherapies for recurrent/metastatic osteosarcoma.
Dr. Hegde will begin working on this project in early 2013 and is funded for the research by CureSearch for Children’s Cancer for two years. During the course of her grant, Dr. Hegde will provide updates on her research, and CureSearch looks forward to sharing those with you.