To model metastases present in the brain before starting ISV + α-CTLA-4 treatment targeting an extracranial tumor, we engrafted mice with a primary right flank B78 tumor, allowed this to grow for 3–4 weeks, then engrafted B78 melanoma (200 000 cells) in the right striatum of the brain 24 hours prior to initiation of ISV + α-CTLA-4 treatment. Here, CTLA4 is linked to melanoma.