kills more than 90 percent
of patients within five years
of diagnosis ( 1).
Pancreatic
Cancer
Special Feature on Immunotherapy
The FDA has also designated lambrolizumab, a second therapeutic antibody that targets PD1, as a
breakthrough therapy for advanced melanoma, after it was reported to benefit patients (114).
Despite the dramatic responses seen in some patients treated with ipilimumab, or an agent targeting PD1
or PDL1, these individuals are a small fraction of the total number of people affected by cancer. Perhaps
the greatest promise of immunotherapy lies in combining immunotherapies that target different immune
checkpoint proteins or immunotherapies that operate differently, as well as combining immunotherapies
with other types of anticancer treatments.
To this end, a recent study suggests that combining ipilimumab and nivolumab shows promise, and a
large-scale trial has been initiated to verify this hypothesis (115). In addition, an early-stage trial found
that combining ipilimumab with sargramostim (Leukine), a synthetic version of an immune-system
boosting substance naturally produced in the body significantly increased overall survival for patients
with advanced melanoma (116). Thus, the potential of combining an immunotherapy that releases the
brakes on the immune system with an immunotherapy that boosts the immune system is immense.
Boosting the Killing Power of the Immune System
To return to the analogy of driving a car, another approach to immunotherapy is to step on the
accelerator, enhancing the ability of the immune system to eliminate cancer cells. This can be done in
several ways, including giving a patient a therapeutic vaccine or a form of treatment called adoptive
immunotherapy.
A therapeutic vaccine trains a patient’s immune system to recognize and destroy their cancer. The only
therapeutic cancer vaccine currently approved by the FDA is sipuleucel-T (Provenge). It is a cell-based
vaccine that was approved in 2010 for the treatment of advanced prostate cancer (117). Each patient
receives a customized treatment that uses immune cells called dendritic cells from their own body to
boost their cancer-fighting T cells. Researchers are currently conducting small clinical trials to examine
whether the effectiveness of sipuleucel-T can be enhanced by combining it with the antihormone therapy
abiraterone (Zytiga) (118).
The development of therapeutic cancer vaccines is an intensively studied area of cancer research. In the
United States alone, there are several hundred ongoing clinical trials testing therapeutic cancer vaccines.
Some are similar to sipuleucel-T, utilizing the patient’s own dendritic cells, and these include one that
has shown early promise as a treatment for colorectal cancer (119). Others operate in different ways,
including one called PROSTVAC, which is being tested in a large clinical trial after early results indicated
that it significantly increased survival for men with advanced prostate cancer (120).
Another therapeutic cancer vaccine clinical trial that has recently reported very encouraging early results
is assessing the effectiveness of a combination of two vaccines, GVAX Pancreas and CRS-207, as a
treatment for advanced pancreatic cancer (121). The two vaccines work together to boost patients’
immune systems in different ways. GVAX Pancreas comprises pancreatic cancer cells that release
GM-CSF, which generally enhances immune system function. CRS-207 is a nontoxic bacterial vaccine
engineered to carry a protein that will boost the killing power of patients’ immune cells. Experiments in
mice originally showed that the combination of GVAX Pancreas and CRS-207 heightens the activity of a
