Poster abstracts
Poster number 2 submitted by Theresa Relation
Mesenchymal Stem Cell Therapy for Interferon-Gamma Delivery in Neuroblastoma
Theresa Relation (Neuroscience Graduate Program), Tai Yi (Center for Cardiovascular Research, The Research Institute at Nationwide Childrens Hospital), Adam Guess (Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Childrens Hospital), Satoru Otsuru (Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Childrens Hospital), Christopher Breuer (Center for Cardiovascular Research, The Research Institute at Nationwide Childrens Hospital), Ed Horwitz (Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Childrens Hospital)
Abstract:
The standard of care for neuroblastoma, the most common extracranial solid tumor in childhood, consists of surgical resection, chemotherapy, and radiotherapy. While low-risk patients often achieve long-term survival, high-risk patients will frequently relapse with aggressive, therapy-resistant tumors. Moreover, we currently lack established, effective therapies for these patients; hence, long term survival remains below 50 percent. One promising treatment strategy is the delivery of anti-tumor therapeutic agents via cell therapy. Mesenchymal stem cell (MSC) therapy has been utilized to treat diseases such as osteogenesis imperfecta, cardiovascular diseases, osteoarthritis, autoimmune diseases, and cancer. In this study, we use MSCs to deliver the pro-inflammatory cytokine interferon-gamma (IFNγ) to the microenvironment of intra-adrenal neuroblastoma. IFNγ has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME), which supports and protects tumor cells through physical and cellular barriers to cancer-targeting therapy. However, clinical trials have failed to demonstrate efficacy of systemic IFNγ therapy due to the high concentration of IFNγ required and associated toxicities. By using MSC therapy to deliver IFNγ locally to the tumor, we anticipate achieving a high TME concentration of IFNγ while maintaining safe levels in circulation. By increasing immune activation, we hypothesize that IFNγ MSCs will increase immune cell infiltration into the tumor for more efficient tumor antigen recognition and cell-mediated killing. In the presented work, the preliminary results of this study are examined, including vector design/generation and establishment of animal model, and future directions are explored.
Keywords: interferon-gamma, neuroblastoma, mesenchymal stem cells