Phoenix Children's Hospital Archives - Page 2 of 2

2014

Impact Grant

Dr. Pooja Hingorani

Phoenix, AZ

Title: Blockade of Programmed Death Receptor Pathway as a Therapeutic Strategy in Osteosarcoma

Principal Investigator: Pooja Hingorani, MD; Phoenix Children’s Hospital
Co-Principal Investigator: Joseph Blattman, PhD; Arizona State University

Osteosarcoma (OS) is the most commonly occurring bone cancer in children and adolescents, accounting for approximately 3% of all diagnosed childhood malignancies. Approximately 25-30% of OS patients develop pulmonary metastatic disease, which is associated with very poor prognosis as 5-year survival rates for these patients are less than 20%. Conventional radiation and chemotherapeutics remain ineffective at curing patients with metastatic OS with surgery being the mainstay of therapy. Moreover, there are long-term detrimental effects associated with chemotherapy including an increased risk of secondary cancers, organ (kidney, heart, hearing) damage, and impaired cognitive abilities. Therefore, the ineffectiveness and associated hazards of conventional therapies necessitate the development of new approaches to treat OS.

The proposed study is a collaborative endeavor between Phoenix Children’s Hospital (PCH) and Arizona State University (ASU) and seeks to evaluate immune modulation as a novel therapeutic strategy in osteosarcoma. Specifically, we will evaluate the effects of blocking immune inhibitory checkpoint programmed death receptor (PD-1) pathway in combination with chemotherapy and other immune therapies in inhibiting growth and development of lung metastases in mouse models of OS.

Both Principal Investigators have designed the study concept. The preclinical work described in the proposal will be conducted in Dr. Blattman’s lab at ASU. The human patient samples will be retrieved from the PCH tissue bank. Data will be reviewed and analyzed by both PIs.

The results of this study will provide the necessary preclinical data to establish the rationale for using the PD-1/ PD-L1 inhibition as a therapy in patients with OS.