This initial body of work culminated in a phase III trial in which CTLA-4 blockade with an anti-CTLA-4 mAb improved overall survival in patients with metastatic melanoma compared to patients receiving a tumor vaccine [54], and to subsequent approval of the anti-CTLA-4 antibody ipilimumab for metastatic melanoma [55]. Here, CTLA4 is linked to metastatic melanoma.