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Preclinical models of melanoma leptomeningeal disease to assess intrathecal checkpoint blockade.


ABSTRACT: Leptomeningeal disease (LMD) is a subtype of central nervous system metastatic disease that is associated with poor patient outcomes and limited treatment options. There is an unmet need to develop preclinical models of LMD to expedite and improve the development of new therapeutics. Here, we describe the development of multiple orthotopic immunocompetent murine models of melanoma LMD, including their use to assess the efficacy of systemic and/or intrathecal immunotherapy. LMD was established by direct intrathecal injection of murine cell lines (B16-F10, BP, D4M, D4M-UV2, MC38-gp100, RMS, YUMM3.1, and YUMMER1.7) into the cisterna magna of C57BL/6 mice. Tumor take rate, distribution, histology, peri-procedural mortality, and animal survival were assessed for each cell line. Intrathecal and

SUBMITTER: Guerrieri RA 

PROVIDER: S-EPMC12491558 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature