​‘Brakes for Breasts’ has been tirelessly raising money for my research program since the publication of my study in 2010 that showed the feasibility of generating a vaccine capable of safely and effectively preventing breast cancer. The ‘Brakes for Breasts’ fundraising efforts started with 5 automotive repair shops in the Cleveland, Ohio area that raised $10,000 in 2011 and has now evolved to incorporate hundreds of shops in the United States and Canada that raised over $250,000 in 2020 and over $1 million since their initial efforts!! ’Brakes for Breasts’ has become the largest third-party fundraising entity at the Cleveland Clinic. More importantly, ‘Brakes for Breasts’ has become an integral partner of our effort to develop the first vaccine designed to prevent triple negative breast cancer, the most aggressive and lethal form of this disease.

​The integral nature of the ‘Brakes for Breasts’ fundraising efforts was particularly highlighted several years ago when I had depleted my external funding support and was sustained only by the resources from ‘Brakes for Breasts’ until I was able to get additional external grant support. It has been one of my unexpected but delightful experiences to be able to share the common vision of a world without breast cancer with ‘Brakes for Breasts’. Vaccines that prevent adult-onset diseases like breast cancer and ovarian cancer will address much needed unmet healthcare needs with the potential to dramatically alter the natural history of these diseases. With all this being said, I am most pleased to announce that our team of basic researchers and clinical investigators have overcome all of the hurdles needed to enter clinical trials and that in December, 2020, the US Food and Drug Administration (FDA) gave us clearance to start our phase I clinical trial. Our current plan is to initiate recruitment of test subjects and vaccination before the end of July, 2021. It has been quite an adventure, but we are finally about to take the first big step toward determining whether we will be able to dramatically change how we control breast cancer. This landmark event would have never occurred without the heroic efforts of Leigh Anne Best and Laura Frank and the enlightened support of the ‘Brakes for Breasts’ program.

​Although we have made substantial progress together, we still have much to do. We look forward to your continued support and to sharing this adventure with all of the ‘Brakes for Breasts’ participants. We anticipate that within a very short time we will be celebrating with you about reaching our long-awaited milestone of initiating clinical trials.

In May, 2010, I published a manuscript in a very prestigious journal called Nature Medicine. The manuscript provided details of a vaccine created in my laboratory and designed to prevent breast cancer. The publication attracted an enormous amount of global media attention, and I was suddenly immersed in media notoriety with numerous interviews about my discovery. This attention was all very unexpected but turned out to be very productive in the sense that it attracted the attention of Leigh Anne Best and Laura Frank. These women had been working hard to raise money for breast cancer but were not happy with conventional breast cancer organizations that were very demanding and used much of their raised money for administrative costs. Leigh Anne and Laura heard about my efforts in developing a novel vaccine designed to prevent breast cancer and found out that 100% of any money that they raised would go directly into my research program with none of the donations going toward any administrative costs. Leigh Anne and Laura found this feature to be very attractive and they subsequently contacted me. The rest is history. In their first year, Leigh Anne and Laura and their Brakes for Breasts program raised about $10,000 from a handful of automotive maintenance shops in the Cleveland metropolitan area. Every year since 2010, Leigh Anne and Laura found a way to raise increasing amounts of money for my program from more and more shops across the nation and even Canada. Their efforts saved my program and kept my research going through many lean years that included being turned down by over 17 grant applications and experiencing a failed business venture. Honestly, I would have had to shut down my research program long ago if it were not for the sustaining yearly support from Brakes for Breasts. Fortunately, in 2016, the Department of Defense requested applications for projects focused on preventing breast cancer because military families have a higher incidence of this disease compared to the general American population. I saw this as a rare opportunity to apply for such focused funding, and I immediately submitted my application for this money by partnering with my colleague G. Thomas Budd, M.D., a breast cancer oncologist at the Cleveland Clinic. We were successful in receiving a four-year award starting November 1, 2017 that provided me with $2.2 million in direct funds for manufacturing the human vaccine and performing toxicology studies to determine its safety in animals. In addition, the award provided Dr. Budd with $1.8 million in direct funds for performing two phase I clinical trials designed to determine the safety of the vaccine in human subjects and the dosage needed to achieve a vibrant anti-tumor immune response. The phase Ia safety and dosage trial will be performed on human subjects recently diagnosed with triple negative breast cancer (TNBC), the most lethal form of breast cancer. The second phase Ib safety and dosage trial will be on human subjects at high risk for developing TNBC who voluntarily elect mastectomy to reduce their risk. We plan to vaccinate these subjects prior to mastectomy and then examine their removed breasts for any inflammatory damage that the vaccine may cause to ensure safety of our vaccine in healthy, cancer-free women. ​

There are two major components of the TNBC vaccine: 1) the target protein, namely, human α-lactalbumin. This is the specific protein against which we plan to induce a well-defined immune response associated with inhibition and prevention of breast cancer growth; and 2) the “adjuvant”, an inflammatory substance that non-specifically irritates and activates what is called the innate immune system that orchestrates the defined specific response to the α-lactalbumin target protein. Both of these components must be made under very detailed and controlled conditions and must meet the very complex analytic requirements of the US Food and Drug Administration (FDA). This analytic process is called Good Manufacturing Practice (GMP). It may sound like a benign name for a manufacturing process, but it is well-known to represent an extremely complicated process that requires a fastidious attention to details that will convince the FDA that our reagents can be produced in a repeatable manner with no chance of containing contaminants that may harm humans injected with the substance. This GMP manufacturing process is extremely expensive and requires specialized facilities specifically dedicated to this effort. Our human α-lactalbumin was made under GMP conditions by a company in California at a cost of approximately $850k. The adjuvant is being manufactured in a GMP facility in Switzerland at a cost of approximately $750k. However, after GMP manufacturing of our adjuvant, we will have additional expenses for performing sterility studies as well as fill and finish studies in vials for use in clinical trials. I anticipate that these costs will exceed $300k. There are several other additional costs related to preclinical toxicology studies and prolonged stability studies that will easily consume the remainder of the $2.2 million allocated from our Department of Defense grant for preparing the vaccine for our clinical trials. 

A few months ago, I was hoping that these GMP products would be ready in time for us to apply to the FDA for permission to start recruiting for our phase Ia clinical trial by the fall of 2020. However, the human race has since been stalked by the SARS-COV-2 virus that has caused the current COVID-19 pandemic. This pandemic has caused unanticipated issues that will likely delay recruitment of test subjects until the first quarter of 2021. While we are waiting for completion of all regulatory requirements, we are currently assembling our application to the FDA to obtain permission to use our Investigational New Drug (IND) in clinical trials.

I have provided only the core basic things that must be done to get permission from the FDA to test our vaccine in human subjects. I simply want to give you an idea how complicated this process is and why it takes so long and costs so much. Meanwhile, when travel becomes acceptable again, I am hoping to attend appropriate meetings to inform the medical research community about what we are doing. In addition, we have submitted several grants for supporting our lab work and have submitted several patent applications to obtain sufficient intellectual property (IP) protection to attract commercial licensing partners from the pharmaceutical/biotech industry. The latter is necessary to provide a licensing partner with a monopoly to develop and test our vaccines in very expensive advanced phase II/III clinical trials to determine whether our vaccine is effective in inhibiting the growth and emergence of breast tumors and whether it has potential for commercialization. Without the expensive IP in the form of several patents that cover all industrialized countries, our vaccines would be in the public domain without any possibility of receiving interest from the pharmaceutical/biotech industry. Basically, it would be dead and finished. Thus, strong IP is an essential but costly part of our overall effort to provide the general public with our vaccine. The expenses for patent protection have been absorbed by the Cleveland Clinic. Our strong IP has worked since we formed a strategic alliance and licensing arrangement with Anixa Biosciences, Inc. (ANIX) on July 17, 2019 (https://www.crainscleveland.com/health-care/anixa-biosciences-cleveland-clinic-enter-license-agreement-breast-cancer-vaccine). This arrangement will provide us with access to investor money needed to finance our very expensive phase II/III clinical trials. I must emphasize that this licensing agreement provided absolutely no money or other assets to me or to my research program. 

In addition to all of the ongoing efforts to move our TNBC vaccine through the FDA regulatory process, we are finishing the preclinical testing of our preventive ovarian cancer vaccine. This vaccine, like the TNBC vaccine, can also be used effectively to treat established growing ovarian tumors and will have to go through two phase I trials similar to the clinical plan we have for our TNBC vaccine. Currently, I have no funding for these clinical trials and am actively seeking such funding. 

Finally, I would like to inform you that I must rely on philanthropy for paying the modest salaries of the laboratory and regulatory personnel involved in getting our vaccine ready for clinical trials. These salaries were not included in the DoD grant because of the limits the DoD provided for funding this project. I would greatly appreciate continued support from Brakes for Breasts to cover all of the unfunded expenses involved in our very expensive clinical trials designed ultimately to prevent TNBC and ovarian cancer and thereby profoundly alter the natural history of these lethal diseases.

1)PROGRESS OF THE VACCINE OVER THE PAST 10 YEARS

2)CURRENT STATUS OF THE VACCINE

3)QUOTE ON THE IMPORTANCE OF THE FUNDS RAISED

“We are on the verge of testing our breast cancer vaccine in clinical trials, and philanthropy has been the foundation of this progress. Without the extensive and generous support I have received from Brakes for Breasts, I would have had to end my research on immune prevention of breast cancer several years ago. My entire team believes that we are doing transformative work that has the potential to dramatically change the way we control breast cancer. I think it will all be very worthwhile, and I look forward to a great celebration together.”

Mort and Iris November Distinguished Chair in Innovative Breast Cancer Research Staff,

Dept. of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Professor,

Dept. of Molecular Medicine, Lerner College of Medicine of CWRU

Email: tuohyv@ccf.org; Cell: 216-213-8734