James Allison, at the University of California, Berkeley, discovers in the early 1990s that the CTLA-4 protein, present on the surface of the immune system's T cells, acts as a molecular "brake" that limits the intensity of the immune response, an evolutionarily necessary mechanism to prevent the immune system from attacking the body itself, but one that can also limit the immune system's ability to effectively attack cancer cells. Allison develops an antibody capable of specifically blocking the CTLA-4 protein, releasing that brake and allowing T cells to attack the tumor more intensely, demonstrating in 1996 that this approach completely eliminates tumors in laboratory mice. Tasuku Honjo, at Kyoto University, independently discovers in 1992 a different protein, PD-1, that acts as a second, distinct immune brake, and develops in parallel an equivalent therapeutic approach based on blocking this protein. Both approaches — targeting distinct molecular brakes of the immune system, jointly called "immune checkpoints" — translate into clinically approved drugs from 2011 onward, radically transforming the treatment of numerous types of cancer that previously had very limited prognosis, including metastatic melanoma, by achieving durable remissions in some patients through the patient's own immune system reactivated against the tumor, rather than directly attacking cancer cells with conventional chemotherapy or radiotherapy.