Dear Friends,
I have been asked by Uschi Keszler, founder of Pennies in Action, to
field some often-asked questions regarding the exciting breast cancer vaccine
initiative that she and her organization are supporting. As an experienced
Immunologist, and one who has had some involvement in the development of this
approach, I feel that I am in an excellent position to offer my personal
thoughts and opinions on why this matter should be worthy of your attention and
support.
What is this all
about? Dr. Brian Czerniecki and his team of investigators have developed a
vaccine strategy for secondary prevention of breast cancer. Secondary
prevention is the capacity to prevent the recurrence of cancer once the primary
tumor has been identified and surgically eliminated. This vaccine strategy
temporarily removes some of the breast cancer patient’s own white blood cells
prior to surgery. During a 2-day period outside the body the cells are exposed
to breast cancer proteins as well as biochemical signals that mimic infection.
The cells are then re-administered back to the patient each week for 4-6 weeks
prior to the scheduled surgery. The re-introduced white blood cells then signal
the body’s immune system to attack the cancer. Whatever remains of the tumor is
then surgically removed and the patient is closely followed to monitor for
recurrence of disease. When non-vaccinated patients receive the best current
standards of care after surgery (including local radiation and chemotherapy),
tumors still recur in up to 20-25% of the patients within 5 years. Reducing
this number with a vaccine would be the most cost-effective and humane way to
prevent all of the morbidity and mortality that occurs as a result of breast
cancer recurrence after surgery. This includes local recurrence, metastatic
disease, death due to advanced cancer, and all of the financial cost and
side-effects of chemo- and radiation therapy.
Why focus on
preventing recurrence? Why not develop a vaccine to prevent breast cancer in
the first place? It is very difficult to predict who, among those who have
never had breast cancer, will develop it within a 3-5 year window. Testing an
experimental vaccine for primary prevention would therefore require the
immunization of thousands of individuals in order to catch the handful that
would otherwise develop it. Such a large trial would be financially
prohibitive. On the other hand, individuals who have already developed a
high-grade early breast cancer, and had it surgically removed, are at
considerable risk for experiencing a recurrence in 3-5 years. By focusing on
this high-risk group, it will require fewer vaccinated patients to prove that
immunization suppresses recurrence rates. Such a smaller trial is of course
more
financially manageable. However, it should be noted that a vaccine that
is proven to prevent recurrence would almost certainly also prevent cancer from
ever developing in the first place. Therefore the development of a vaccine that
prevents recurrence shortens the path to achieving true cancer prevention.
Does Dr.
Czerniecki’s vaccine show any sign of providing secondary protection? In two “phase 1-2”
clinical trials conducted at the University of Pennsylvania, over 50 women were
vaccinated. Some of these women have
been followed out beyond 88 months (over 7 years). In the subset of women whose
breast cancers did not express the estrogen receptor (about half), absolutely no recurrences have been observed.
Blood samples taken from women up to 5 years after vaccination demonstrate
white blood cells that still respond against breast cancer proteins, indicating
a very long-lived immune response, which is necessary to provide extended
protection from recurrence.
In what way are
these results exciting and different from other breast cancer vaccines I have
heard of? First, Dr. Czerniecki has over a seven-year track record of immunizing
real people with breast cancer using this vaccine. This is not a pie-in-the-sky
idea that has been tried only “in the test tube” or in mouse models. The vaccinated
patients have had real, tangible results. Seven of the patients, when sent to
surgery after receiving the course of vaccinations, had no detectable cancer
left in their breasts. Several of the patients showed such a large degree of
tumor shrinkage that the remaining disease could be safely removed using a
lumpectomy procedure, rather than having to remove the whole breast. Past
attempts by others to produce anti-cancer vaccines show that immunity wanes a few
weeks after vaccination. The responses from Dr. Czerniecki’s vaccine have been
shown to last for years, potentially offering patients long-term protection
from recurrent tumors. Finally, there have been no recurrences in a large
subset of our patients. No current therapy, established or experimental, has
ever shown this level of prevention. The results of these trials have been
published in peer-reviewed journals including Cancer Reserarch (2007), Cancer
(2012) and the Journal of Immunotherapy (2012).
Why are these
results so good? The body’s immune system is primarily designed to attack
microbes (bacteria and viruses). Dr. Czerniecki’s vaccine strategy is unique in
that it, by design, “tricks” the immune system into responding against cancer
as though it was a dangerous infection. In addition, we are attacking the
breast cancer at a very early stage. Remember, the common vaccines against
infections that you are familiar with are all preventative. They don’t work
once you are already sick. The medical establishment has become very good at
detecting breast cancer at earlier and earlier stages. Unfortunately, women
with one bout of breast cancer are at high risk for recurrence. The challenge
therefore is to develop treatments that will preserve the health of the patient
in the long-run without the debilitating and dangerous side-effects of
radiation therapy and chemotherapy.
What is the next
step? In order to gain approval from the FDA for using this vaccine as a
standard therapy, a successful “Phase 3” trial must be completed. Such a trial
will be conducted at multiple institutes (so that other groups of physicians
can replicate the University of Pennsylvania results), and must involve a
larger number of patients (around 200, so that statistics can prove
conclusively that we are really preventing recurrence). We can begin such a
trial almost as soon as we secure the necessary funds.
If these results
are really so good, why hasn’t money already been obtained for the phase 3
trial? The first two phase 1-2 trials were generously supported by prestigious
“R01” awards from the National Institutes of Health, which funds the bulk of
health-related research conducted at Universities and Biomedical Research Institutes
across the United States. Unfortunately, NIH “caps” their awards at $500,000
per year for 4-5 years (2-2.5 million per grant, maximum). Such funds can
support early trials involving 30-40 subjects, but we calculate that a
multicenter phase-3 trial will cost around 4-6 million dollars. The NIH simply
does not have a common funding mechanism that covers something this large.
Likewise, private funding organizations such as the American Cancer Society and
the Susan G. Komen Foundation place most of their emphasis on awards of similar,
smaller scale.
Another avenue would be the formation of a startup company and the
attraction of venture capital. Unfortunately, the cancer therapy options that
are most profitable are not necessarily the ones that are best and most
desirable from the standpoint of the patient. Outside investors may not be able
to resist selling out to a generous offer from a large pharmaceutical company.
The pharmaceutical company may in turn decide that there is more money to be
made selling standard chemotherapy than preventative vaccines and “shelve” their
newly-acquired technology. Dr. Czerniecki and his colleagues strongly believe
in the entrepreneurial spirit that drives innovation in the United States, but
we must acknowledge that we should first strive for a transparent, fully
independent demonstration of the vaccine’s effectiveness. Only after the
vaccine’s value is common knowledge, and there is considerable demand from the
public for this new preventative, should the technology be transferred to
business interests. This approach will ensure that the vaccine eventually gets
to the people who need it.
Will this vaccine
have a large impact on health? Our “proof-of-principal” vaccine is
directed at a single protein called HER-2 that is produced by about 30% of all
individuals with breast cancer. We are already planning a strategy to expand
and improve the vaccine therapy to increase the number of individuals who would
benefit from immunization. First, we are pairing vaccination with a short
course of the anti-estrogen drug Tamoxifen. Early studies suggest that this
combination may improve overall effectiveness for individuals with cancers
expressing the estrogen receptor. Second, we are laying the scientific
groundwork for including additional cancer-related proteins such as HER-1 and
HER-3. A vaccine formulation including HER-1, 2 and 3 could potentially allow
protection of up to 90% of breast cancer patients. Perhaps even
more important, these cancer-related proteins are also found on other
common cancers including cancer of the lung, pancreas, ovary, colon and
prostate. This means that when fully developed, this vaccine technology has the
potential to impact some of the most common tumor types.
I hope that I have answered most of your questions, and that you find
this cause worthy of your support.
Sincerely,
Gary K. Koski, Ph.D.
Associate Professor of
Biological Sciences
Kent State University
Kent, Ohio 44242
