CTLA4 and metastatic melanoma: Large phase I studies led to the prompt approval of the anti-PD-1 monoclonal antibodies pembrolizumab (humanized IgG4, Merck) and nivolumab (fully human IgG4, Bristol-Myers Squibb, Ono Pharmaceuticals) for patients with unresectable or metastatic melanoma not responding to anti-CTLA-4 (17–19).