Spring 2022 Program Update
It has been a while since I wrote you a formal update on the progress we have made with respect to moving our vaccine technologies from what seemed like endless preclinical development to actual testing in human clinical trials. I know that you have already heard about this, but I cannot adequately express my excitement in formally announcing that we vaccinated the first woman with our breast cancer vaccine on October 26, 2021. All of the bureaucratic and regulatory issues that had to be addressed were finally completed, and my colleague and principal clinical investigator, Dr. G. Thomas Budd, was able to start our Phase Ia clinical trial.
I am pleased to say that at this time we have vaccinated several women, and the trial is going on according to plan. However, I am not allowed to say anything further about it and in reality, I really don’t know much more that I have already stated here. The title of the Phase Ia clinical trial is: “Adjuvant Therapy with an Alpha-Lactalbumin Vaccine in Triple-Negative Breast Cancer”, and the details of the Phase Ia trial plan can be found here: https://clinicaltrials.gov/ct2/show/NCT04674306. This Phase Ia trial is designed to determine the correct dose and the safety profile of our breast cancer vaccine. It is not powered with enough test subjects to determine whether the vaccine actually prevents TNBC or prevents the recurrence of TNBC. This clinical trial is simply the first step needed before moving ahead in more advanced clinical trials that will ultimately determine whether our vaccine actually has the ability to safely and effectively prevent TNBC.
After we establish the correct dose as well as a safety profile acceptable to the FDA for more clinical testing, we will then start our Phase Ib clinical trial in women at high risk for developing TNBC and who have elected voluntary bilateral mastectomy to reduce their risk. About 50 of these procedures are performed annually at the Cleveland Clinic, and we plan to vaccinate consenting women prior to their mastectomy so we can examine the breast tissues extensively for any damage that the vaccine may cause. We are hoping to start this Phase Ib safety trial before the end of 2022. Once we have determined that the vaccine is safe in humans, we can begin to vaccinate cancer-free women as part of the more advanced phase II/III trials to determine efficacy of the vaccine.
We have submitted an abstract (#TPS1125) outlining the design of the Phase Ia trial to the Annual Meeting of the American Society of Clinical Oncology (ASCO), and the presentation, titled "Phase 1 Trial of an Alpha-Lactalbumin Vaccine in Patients with Moderate- to High-Risk Operable Triple-Negative Breast Cancer (TNBC)" will be presented by Dr. G. Thomas Budd during the June 3-7, 2022 meeting in Chicago, IL.
I would also like to bring you up-to-date on our ovarian cancer vaccine. As you likely already know, we have developed a vaccine designed to prevent epithelial ovarian carcinoma (EOC), the most common form of ovarian cancer and the most lethal of all female-specific malignancies. On January 11, 2021, I submitted an application to the PREVENT Program sponsored by the National Cancer Institute’s (NCI) Division of Cancer Prevention (https://prevention.cancer.gov/major-programs/prevent-cancer-preclinical-drug-development-program) to obtain their support in developing our EOC vaccine. On April 15, 2021, I received a letter indicating that the NCI PREVENT Program would provide the resources to bring our vaccine through the early Phase I/II clinical trial process. However, they are obligated first to repeat our results. When they do so, they will proceed with the very expensive process of completing the preclinical development that requires very detailed manufacturing, toxicology, etc. according to the regulatory specifications of the Food and Drug Administration (FDA) before actually testing the ability of the vaccine to prevent EOC in women at high-risk due to carrying mutations in their BRCA1 and/or BRCA2 genes. This is a special kind of support that is clearly worth several million dollars. However, none of the money comes to my research program, and the role for me and my lab members is to serve as “non-paid consultants” in order to make the project successful. “Non-paid” means that the NCI doesn’t pay us, but I still have to pay myself a large part of my own salary as well as the complete salaries for all of my employees. This situation highlights the role of philanthropy in making sure that all this will happen and that we will be able to create a 21st century vaccine program that prevents these adult-onset cancers from occurring. This is and always has been the commitment that I have made to you. I will continue to do so as long as I have the resources that ensures that such dreams become reality.
I cannot adequately express my gratitude to you for your support during all these years of development and for sharing this journey. Primary immune prevention of adult-onset cancers is both feasible and necessary. I can only reiterate what I have said so many times that this work could not have reached this stage without your generosity. I am personally most grateful as are all members of my research and clinical teams for the opportunities made possible by your generous support that continues to be a source of hope for individuals and families whose lives have been touched by breast cancer and ovarian cancer.
Vincent K. Tuohy, Ph.D.
Mort and Iris November Distinguished Chair in Innovative Breast Cancer Research Staff, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Professor, Molecular Medicine, Cleveland Clinic Lerner College of Medicine of CWRU
P.S. ‒ We continue to get a considerable amount of media attention for our work. For your perusal, I have added a list below with the URLs indicating much of the attention we received since October 26, 2021.
WOIO-TV 19, Fox News Affiliate, Cleveland, OH
Breast Cancer Vaccine Study Underway, WOIO-TV 19, Fox News Affiliate, Cleveland, OH, by Katie Tercek; October 26, 2021
New Breast Cancer Vaccine Trial Underway at Cleveland Clinic, Researchers Announced on Tuesday That They Have Started a Phase 1 Vaccine Clinical Trial in the Fight against One of the Deadliest Forms of Breast Cancer: Triple Negative Breast Cancer, People Magazine, by Tristan Balagtas; October 26, 2021
Cleveland Clinic Consult QD Article
Cleveland Clinic Launches First-of-its-Kind Preventative Breast Cancer Vaccine Study: Retired-Protein Strategy Represents New Approach to Immunization, Cleveland Clinic Consult QD Article; October 26, 2021
Breast Cancer Vaccine - How Does It Work?, YouTube; October 26, 2021
Yahoo News (AXIOS)
Cleveland Clinic to Launch "First-of-Its-Kind" Preventative Breast Cancer Vaccine Trial, Yahoo News (AXIOS), by Shawna Chen; October 26, 2021
Telemundo New York (47)
Breast Cancer Vaccine Could Be Reality Soon: Researchers are Advancing the Development of This Promising Vaccine, Telemundo New York (47), by Yolanda Vasquez;, October 27, 2021
Cleveland Clinic Is Researching a 'Breast Cancer Vaccine'—Here's What That Means, and When It Will Actually Be Available, Parade Magazine, by Leigh Weingus; October 30, 2021
Medical News Today
Trials Begin for First Vaccine Candidate to Prevent Triple-Negative Breast Cancer, Medical News Today, by Yasemin Nicola Sakay (fact checked by Alexandra Sanfins, Ph.D.); November 2, 2021
An Exclusive Interview with Dr. Vincent Tuohy: Journey to a Triple Negative Breast Cancer Vaccine, by Judy Fitzgerald from Sisters4Prevention; November 9, 2021
The Doctors TV Show
Could a Preventative Breast Cancer Vaccine be On the Way?, The Doctors, WBNX-TV, Cleveland, Ohio, by Kristi Funk; November 16, 2021
New Study Explores if a Vaccine Can Prevent Breast Cancer, Time Magazine by Alice Park; November 29, 2021
CBS Evening News
Doctors Test Possible Breast Cancer Vaccine, CBS Evening News with Norah O’Donnell, by Tara Narula; December 22, 2021
Press Release from Anixa Biosciences
Anixa Biosciences Announces Japanese Patent on Ovarian Cancer Vaccine; Preclinical Work for the Prophylactic Vaccine, Invented and Developed at Cleveland Clinic, is Ongoing with Support from the National Cancer Institute's PREVENT Program, Press Release from Anixa Biosciences; January 25, 2022
Drug Discovery News
Anti-Müllerian Hormone May Be the Next Big Thing in Women’s Health ‒ A Hormone Only Discussed Among Specialized Scientists is Making a Big Splash in the Ovarian Health Field ‒ It May Soon Become a Household Name, Drug Discovery News, Volume 18, Issue 2; by Natalya Ortolano; February 8, 2022
News5Cleveland, ABC News Affiliate, Cleveland, OH
New Breast Cancer Trial Underway at Cleveland Clinic, Targets Most Aggressive Form, News5Cleveland, ABC Affiliate, Cleveland, OH, by Tracy Carloss; March 22, 2021
New Generation of Cancer-Preventing Vaccines Could Wipeout Tumors Before They Form: Shots Enter Early Clinical Trials for Healthy People at High Risk for Disease, Science, Volume 376, Issue 6589, by Jocelyn Kaiser; April 7, 2022
Press Release from Anixa Biosciences
Anixa Biosciences Announces Presentation on Breast Cancer Vaccine Trial at the American Society of Clinical Oncology (ASCO) Annual Meeting, Press Release from Anixa Biosciences; April 28, 2022
WKYC-TV Interview by Dave Chudowsky; I was interviewed last week by Dave Chudowsky; the interview will be aired sometime next week; I will let you know what day and time as I find out.
2021 Progress Update for ‘Brakes for Breasts’
‘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.
Vincent K. Tuohy, Ph.D.
“BRAKES FOR BREASTS” ANNIVERSARY
1)PROGRESS OF THE VACCINE OVER THE PAST 10 YEARS
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.
2)CURRENT STATUS OF THE VACCINE
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.
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.”
Vincent K. Tuohy, Ph.D.
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: [email protected]; Cell: 216-213-8734
Information About the Breast Cancer Vaccine Research Program
Dr. Vincent Tuohy
In Spring 2017, Dr. Tuohy’s research program was awarded funding to launch a greatly anticipated clinical trial to begin testing the vaccine. The goals of this trial will be to determine proper dosage as well as safety parameters of the vaccine including risks and side effects; however, there are a few critical steps the team must accomplish to achieve regulatory compliance necessary for human testing. Prior to clinical trials, the Federal Drug Administration (FDA) requires that the investigational new drug (IND) must meet stringent criteria for use in humans. This is done to ensure that the components of the IND are properly made in a reproducible manner and is well defined, pure, and free from contaminants that could harm test subjects. From start to finish, this process is costly (~$1.5-2M) and requires specialized, offsite facilities dedicated to this effort. After this is complete, the team will submit an application to the FDA to obtain permission to use the IND in clinical trials. The first Phase I trial, slated to begin in mid 2020, will focus exclusively on women who have recently recovered from treatment for triple-negative breast cancer, the most lethal form of this disease. If this trial indicates that the vaccine has an acceptable safety profile, it will be followed by a second Phase I trial, which will be open to women at high risk for triple-negative breast cancer who elect voluntary mastectomy to reduce their risk. Dr. Tuohy’s team plans to vaccinate them a few months prior to their planned mastectomy and then examine the removed breast tissues for any inflammation that the vaccine may induce. Once Dr. Tuohy and his team have determined the vaccine is safe in humans, they can begin to vaccinate cancer-free women.
Dr. Tuohy and his team are incredibly grateful for the passion and advocacy behind this important research initiative. Funding enables the team to expand and accelerate their research goals. We look forward to a world that provides pre-emptive immunity against breast cancer. We can make a difference together.
September 2017 IdeaStream Panel Discussion – A Must View! Click Here to Watch Dr. Tuohy and other distinguished Professionals from the Medical Industry
Recent Articles Regarding the Breast Cancer Vaccine and Brakes for Breasts:
2014 Article in Tire Review Magazine
2014 February Tuohy Currents Magazine Article
The Team That Wants To Eliminate Breast Cancer
Brakes for Breasts Initiative Article - Shop Owner Magazine October 2018 Article
FDA Clearance to Initiate Clinical Trial of Breast Cancer Vaccine