EXTH-05. STEM CELL-BASED THERAPEUTIC STRATEGY FOR LEPTOMENINGEAL METASTASIS OF SOLID CANCERS

Abstract Leptomeningeal dissemination (LMD), known as carcinomatous meningitis, 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, their effects are limited, so new therapeutic strategies for LMD are urgently needed. Based on the following greatest advantage of stem cell (SC) based therapeutic strategy for LMD, we tested its efficacy in LMD of various solid cancers; LMD is a condition in which cancer cells spread within a huge single space without separation, and the SCs with the characteristic of cancer tropism and chemotaxis can reach cancer cells easily; Repetitive intrathecal injection of therapeutic agents for patients is an invasive and risky procedure, but SCs can continuously secrete/release therapeutic agents into the cerebrospinal fluid after a few injections and increase local concentration of therapeutic substances. We have shown that treatment using engineered SCs may be effective treatment option against LMD from breast cancer, lung cancer, and malignant melanoma. Specifically, we reported that engineered allogeneic SCs which simultaneously targeting epidermal growth factor receptor (EGFR) and death receptor (DR) has efficacy for LMD of triple negative breast cancer and non-small cell lung cancer. Also, we reported that SCs releasing oncolytic herpes virus, granulocyte-macrophage colony-stimulating factor (GM-CSF), and single-chain variable region fragments (scFv) against programmed death receptor-1 (PD-1) has efficacy in LMD of malignant melanoma. Overall, we believe that SC therapy has the potential to become a new therapeutic option for LMD in the future.