Figure 18: When the Immune System’s Brakes are Applied, Cancers Go. Often when a tumor forms (A), cells of the immune system, called T
cells (multicolored spheres), will attack the tumor (B). When they are successful, the tumor will be eliminated (C). In many cases, however, T cells
are unsuccessful. One reason, among many, is that T cells in the tissues surrounding a tumor often express high levels of molecules that tell T
cells to stop attacking the tumor thus, the immune response is blunted (D), leading to continued tumor growth and ultimately metastasis.
Counteracting these “braking” molecules, which are often called immune checkpoint proteins, is proving effective for the treatment of melanoma
and showing promise for a number of other types of cancer (see Targeting the Immune System to Release Its Brakes, p. 61).
treatment of metastatic melanoma. Ipilimumab releases the
brakes on T cells and significantly prolongs survival ( 100). Some
patients, like Andrew Messinger (who was featured in the AACR
Cancer Progress Report 2011), are still gaining benefit from it more
than three years after starting therapy (101). Ongoing clinical
studies are examining whether ipilimumab might be effective
against other cancers. Early results in patients with advanced lung
cancer are encouraging, but need verification in larger numbers of
The development of ipilimumab highlights the power of continued
investment in research: CTLA- 4 was first identified in 1987, but it
took almost 25 years of scientific endeavor before it became an
FDA-approved therapeutic target. In addition, the tremendous
success of this novel therapeutic antibody has inspired the ongoing
development of therapies directed toward other immune
checkpoint proteins, including one called programmed death- 1, or
PD1 (see Sidebar on Immune Checkpoint Therapeutics, p. 63).
The effects of a therapeutic antibody that targets PD1, as well as
one that targets the protein to which PD1 attaches, called PDL1,
are currently being assessed in clinical trials. The early results are
very promising (103, 104) and indicate that ipilimumab has blazed
the way for a family of similar effective therapies.
Targeting the Immune System to Boost Its Killing Power
Another recent development in immunotherapy for cancer
treatment is using strategies to enhance the ability of a patient’s
own immune cells to eliminate cancer cells. This can be done in
several ways, including giving a patient a vaccine to program their
own immune system to recognize and destroy their cancer or by
growing the patient’s immune cells in the laboratory and
reprogramming them to recognize and destroy their cancer. The
latter are treatments collectively called adoptive immunotherapies.
Sipuluecel-T (Provenge) is the only FDA-approved therapeutic
cancer vaccine. It is used to treat metastatic castration-resistant
prostate cancer, after it was shown to prolong patient survival