EXTH-01. STEM CELL THERAPY FOR LEPTOMENINGEAL DISEASE

Abstract

Abstract Leptomeningeal disease (LMD), known as carcinomatous meningitis, occurs in approximately 5% of all cancer patients. LMD presents an extremely poor prognosis, with an average life expectancy of 4-6 weeks. Although, whole brain/spinal cord irradiation and intrathecal injection of anticancer drugs are sometimes performed, the effects are limited, so new therapeutic strategies for LMD are urgently needed. We have reported that treatment using engineered stem cells (SCs) may be effective treatment option against LMD of breast cancer, lung cancer, and malignant melanoma, which are types of cancer that tends to metastasize to the central nervous system. Specifically, we reported that engineered allogeneic SCs simultaneously targeting epidermal growth factor receptor (EGFR) and death receptor (DR) has efficacy for LMD of triple negative breast cancer. Also, we reported that twin SCs releasing oncolytic herpes virus, granulocyte-macrophage colony-stimulating factor (GM-CSF), and single-chain variable region fragments (scFv) against PD-1 has efficacy in LMD of malignant melanoma. The greatest advantage of SC based therapeutic strategy for LMD is summarized by these facts: (1) LMD is a condition in which cancer cells spread within a single closed space through cerebrospinal fluid, and the SCs characteristic of homing to tumor cells has an advantage; (2) Repetitive intrathecal injection of drugs for patients is an invasive procedure, but SCs can continuously secrete/release therapeutic agents into the spinal cavity after a single injection. We believe that stem cell therapy has the potential to become a new therapeutic option for LMD in the future.