In 1993, Mak received support from the world's largest independent biotech company, Amgen, to establish the Amgen Research Institute in Toronto. Financial support from Amgen resulted in his lab pioneering the use of knockout mice, and as a result his lab generated one of the first knockout mice and has generated more knockout mice than any other lab in the world. Mak’s role in advancing the use of genetically-altered mice in scientific study has led to important breakthroughs in immunology and understanding cancer at the cellular level. As of 2005, Amgen-produced papers have been cited more than 40,000 times. The basic research in cancer conducted by Mak has been published in top international scientific journals and he has given several keynote addresses at cancer symposia across Canada and the United States. By 1995, Mak had reached a high point in his career, when he and his team published their seminal findings on the function of CTLA-4, thus paving the road for Immunotherapy and Checkpoint inhibition as potential anti-cancer therapies.