
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.130
vdae090.130
Final Category: Translational Science
AcademicSubjects/MED00300
AcademicSubjects/MED00310
TRSC-01 STEM CELL THERAPY HAS EFFICACY FOR LEPTOMENINGEAL DISSEMINATION OF DIVERSE TYPES OF SOLID CANCERS
Kitamura Yohei Keio University School of Medicine, Tokyo, Japan

Kanaya Nobuhiko Okayama University School of Medicine, Okayama, Japan

Moleirinho Susana Brigham and Women’s Hospital, Boston/MA, USA

Tamura Ryota Keio University School of Medicine, Tokyo, Japan

Ueda Ryo Keio University School of Medicine, Tokyo, Japan

Sasaki Hikaru Tokyo Dental College Ichikawa General Hospital, Ichikawa/Chiba, Japan

Toda Masahiro Keio University School of Medicine, Tokyo, Japan

Shah Khalid Brigham and Women’s Hospital, Boston/MA, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i39i40
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Leptomeningeal dissemination (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. While treatments such as whole brain/spinal cord irradiation and intrathecal injection of anticancer drugs are sometimes performed, their effects are limited, which urgently necessitates new therapeutic strategies for LMD. We evaluated the efficacy of a stem cell (SC)-based therapeutic strategy for LMD in various solid cancers based on two primary advantages: (1) LMD is a condition where cancer cells spread within a single closed space without separation, and SCs with cancer tropism and chemotaxis can easily reach these cells; (2) Repeated intrathecal injections of drugs are invasive and risky, but SCs can continuously secrete therapeutic agents into the cerebrospinal cavity after a few injections, increasing local concentrations of these substances. Our findings suggest that treatment using engineered SCs may be an effective option against LMD from breast, lung, and malignant melanoma, which are types of cancer that tend to metastasize to the central nervous system. Specifically, we found that engineered allogeneic SCs simultaneously targeting epidermal growth factor receptor (EGFR) and death receptor (DR) have efficacy for LMD of triple negative breast cancer and non-small cell lung cancer. In addition, twin 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) show encouraging results in managing LMD in cases of malignant melanoma. We believe that SC therapy has the potential to become a new therapeutic option for LMD in the future.
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