Establishing An Orthotopic Mouse Model For Evaluating Efficacy Of Cancer Vaccine Against Leptomeningeal Melanoma

Leptomeningeal melanoma (LMM), developed from metastasis of extra cranial melanoma or from residential melanocytes, occur in up to22%of melanomal patients with poor prognosis.In this experimental study we established a brain LMM mouse model by using a self-modified Hamilton syringe and inoculating the B16cells directly into subarachnoid space through a drilled hole in skull in C57BL/6mice.35%to40%of the mice developed melanomas on cerebrum or cerebrum and cisterna magna,10%on cerebrum and cerebellum and15%in cistern magna and on spinal cord. The developed melanomas exhibited as a black gelatinous mass on the cerebral hemispheres surfaces about1.5×1.3×1.0cm in size, and possessed more elevated and condensed nodules. No melanoma was visible in the leptomeninges of the brain bases or within parenchyma of the brain and spinal cord. Histopathologically, the melanoma tissue was filled with intensively grown B16cells and vigorously developed blood vessels, no melanoma cells were observed in brain tissue and the melanoma cells were widely infiltrated in pia matter meningeal layer. Clinically, correlations between the tumor location and detectable signs/symptoms of the mice were found to be compatible with that in the patients with LMM. To test the feasibility of the mouse model, we also tried to immunize the model mice with tumor cell lysate (TCL) prepared from cultured B16cells to induce anti-LMM immunity.