powering cures, realizing futures



Dr. Eugenie Kleinerman
Basic Science Research Grant
– Osteosarcoma

MD Anderson Cancer Center

md anderson cancer center

Eugenie Kleinerman, M.D., Professor of Pediatrics Research, has translational interests in the development of novel therapies for children with sarcomas, particularly osteosarcoma lung metastases.

A Novel Dendritic Cell Vaccine and anti-PD1 for Osteosarcoma Therapy

The University of Texas MD Anderson Cancer Center focuses on delivering world-class patient care through clinical breakthroughs and multidisciplinary approaches to care. Although we are the leaders in adult oncology care, we also strive to use the power of our research and expertise to transform the lives of pediatric patients. Caring for future generations enables us to think towards tomorrow and the breakthroughs that lie ahead.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, adolescents and young adults — it is also a long-standing focus of research efforts at MD Anderson Children’s Cancer Hospital. In the U.S., annual diagnoses have risen to around 800 new cases each year. The five-year survival rate for patients with localized osteosarcoma hovers around 65 percent. Once the original tumor metastasizes, that rate drops to 30-40 percent.

Altering chemotherapy, including dose intensification, has not improved the 65% survival rate for children, adolescents and young adults (AYAs) with osteosarcoma. The survival for patients with metastases and those that relapse after chemotherapy is less than 20%. Genomic analysis has been unsuccessful in identifying consistent targetable options and there were no responses in relapsed/refractory OS patients treated in numerous Phase I or II trials. Identifying new therapies is imperative. Immunotherapies such as dendritic cell vaccines (DCV) and checkpoint inhibitors (anti-PD-1, anti-CTLA-4) have shown activity against adult cancers, but there are no studies in children or AYAs with OS.

Dr. Kleinerman has translational interests in the development of novel therapies for children with sarcomas, particularly osteosarcoma lung metastases. Dr. Kleinerman and her team demonstrated the efficacy of anti-PD-1 therapy against OS lung metastases. Stephanie Watowich, PhD, Professor, Department of Immunology has shown that the activity of DCV can be improved by anti-PD-1 and anti-CTLA-4. Funding provided by the Pediatric Cancer Research Foundation will support Drs. Kleinerman and Watowich investigate whether a unique molecularly engineered DC vaccine that augments T-cells is effective against primary and metastatic OS using preclinical mouse models, and whether its activity can be augmented when combined with checkpoint inhibitors. Preliminary data show vaccine activity in mouse OS models.

The combined expertise of Dr. Kleinerman and Dr. Watowich, mouse models, tumor immune response, immunotherapy, vaccine development, and translational research are unprecedented. This critical effort has the potential to identify new therapeutic approaches for treating children and adolescent and young adults (AYAs) with relapsed/metastatic and primary OS. If efficacy is demonstrated, this approach can be translated into a clinical trial for children and AYAs with OS lung metastases. Demonstrating the preclinical activity of a novel DC vaccine combined with a checkpoint inhibitor will provide a unique new immunotherapeutic approach to treat primary and metastatic OS. Another goal is to combine with chemotherapy for newly diagnosed patients to improve disease-free survival.

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