40 AACR Cancer Progress Report 2013
A protein that attaches to
a defined molecule on the
surface of a cell. These
agents can exert anticancer
effects in several different
Special Feature on Immunotherapy
Figure 13: Stepping Toward the First Checkpoint Blockade. Ipilimumab (Yervoy) is an immunotherapy that works by counteracting brakes on
the immune system called immune checkpoint proteins. It was the first drug of its kind to be approved by the U.S. Food and Drug Administration
(FDA). Almost 25 years of basic, translational, and clinical research underpinned the development of ipilimumab. The story began in 1987, when
researchers discovered a gene that they called CTLA4. It then took nearly eight years before the function of CTLA4 was uncovered, and another
16 years before this knowledge was translated into ipilimumab. There are now several other drugs in development against another checkpoint
protein called PD1 (see Table 9, p 41).
surface high levels of molecules that act like brakes, making the T cells slow down and stop acting
aggressively. This finding led researchers to seek ways to counteract these molecules, which are called
immune checkpoint proteins.
The story of immune checkpoint proteins began in 1987, when researchers discovered a gene that they
called CTLA4 (105) (see Figure 13). However, it took nearly eight years before the immune checkpoint
function of CTLA4 was uncovered, and another 16 years of basic and clinical research before this
knowledge was translated into a clinically effective therapy: a therapeutic antibody that targets CTLA4,
ipilimumab (Yervoy). Upon attaching to CTLA4 on the surface of patients’ T cells, ipilimumab releases the
T cells’ brakes, spurring them into action. This significantly prolongs survival for patients with metastatic
melanoma (106). Ipilimumab was the first treatment in history to improve survival for patients with
metastatic melanoma, and the FDA approved it for this use in March 2011.