Ipilimumab, which targets an immune checkpoint protein
called CTLA- 4, significantly prolongs survival in patients with
metastatic melanoma. This success led to the development of
therapies that target another immune checkpoint protein,
called programmed death- 1, or PD1, as well as those that
target the protein to which PD1 attaches, PDL1. These have
been tested in early stage trials with some success.
A recent small-scale trial of 296 patients showed that an
antibody to PD1 on the surface of immune cells, called T cells,
was able to produce complete or partial elimination of tumors
in 18% of non-small cell lung cancer patients, 28% of
melanoma patients, and 27% of renal cell cancer patients.
Perhaps most importantly, the reduction in tumors lasted for
at least a year in nearly 65% of responding patients (103).
Similarly, a phase I trial of 207 patients treated with an
antibody to PDL1 produced complete or partial elimination of
tumors in 17% of patients with melanoma, 11% of renal cell
cancer patients, and 10% of non–small cell lung cancer.
Further, in patients followed for more than one year, at least
50% had reductions in tumors lasting at least one year (104).
(105). It is a cell-based immunotherapy, wherein each treatment is
customized for the patient and helps direct their immune system to
destroy their cancer cells. While only an early success, it provides
hope that other effective cancer treatment vaccines can be
developed. As such, this is an intensively studied area of cancer
research. In the U.S. alone, more than 300 clinical trials testing
cancer vaccines are actively recruiting patients.
Adoptive immunotherapies are complex medical procedures that
are built upon our accumulating knowledge of the biology of the
immune system, in particular, T cells. The first step is to harvest a
defined population of T cells from the patient. T cells that target the
patient’s cancer are then selected from the harvested population or
generated by genetic engineering, grown in very large numbers and
then returned to the patient’s body, where they fight the cancer.
There are no FDA-approved adoptive immunotherapies, but at the
NCI, one procedure using T cells harvested from a patient’s own
surgically removed tumors has been used to treat metastatic
melanoma for more than 20 years (106). During this period, the
treatment protocol has been refined many times, as scientific and
technological advances have facilitated improvements, and about
20% of patients, including Roselyn Meyer (who was featured in the
AACR Cancer Progress Report 2011), now achieve long-term
remission (107). Despite these successes, the NCI adoptive
American Association for Cancer Research
immunotherapy treatment is not yet considered standard of care; it
remains an area of active research and is only available to patients
enrolled in clinical trials.
The effectiveness of numerous other adoptive immunotherapies is
currently being assessed in various clinical trials for several types
of cancer. Very early clinical studies of an adoptive immunotherapy
for the treatment of chronic lymphocytic leukemia recently showed
that the strategy has tremendous promise (see Sidebar on
Adoptive Immunotherapy for Chronic Lymphocytic Leukemia)
(108), but more patients need to be treated to confirm this.
Additional new adoptive immunotherapies with enhanced ability to
yield patient benefit are likely to emerge in the near future as our
understanding of T cells and how they combat cancer increases.
Directing the Immune System to Cancer Cells
Therapeutic antibodies have been saving the lives of cancer
patients since 1997, when the FDA approved rituximab (Rituxan) for
the treatment of certain forms of non-Hodgkin’s lymphoma. More
than a dozen therapeutic antibodies have been approved by the
FDA for use against several cancers (see Table 6, Appendix) and
many more are in clinical trials.
for Chronic Lymphocytic
A recent report indicates that adoptive immunotherapy holds
promise as a treatment for chronic lymphocytic leukemia
(134). In this study, immune cells, called T cells, were
harvested from three patients and genetically modified in the
laboratory so that they would not only attach to a protein
expressed by the leukemia cells, called CD19, but also be
triggered to attack the cancer cells when they did so. The
number of modified T cells was expanded in the laboratory
before they were returned to the patients. These cells were
still detectable and functioning as expected in the patients six
months later. Moreover, the patients were still in remission at
the time the report was published, which was 10 months after