Sunday, August 19, 2012

Not all vaccines are created equal....!!!!

make sure you watch this video !!!!!

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.

Gary K. Koski, Ph.D.
Associate Professor of Biological Sciences
Kent State University
Kent, Ohio 44242