Right now, human clinical trials for a preventative pancancer vaccine from Calviri are on the horizon, a follow up to currently ongoing canine clinical trials of the same treatment with insofar positive results. If the outcome is good, what we’ll have won’t be a cure for cancer, but instead a way to stop it from ever happening. And it almost didn’t happen. Here, Stephen Albert Johnston, CEO of Calviri, tells the story of the hopeful preventative cancer vaccine that almost wasn’t, and the young company born from a long and sometimes unforgiving journey.
A vaccine for cancer: “Everyone is saying it’s impossible, let’s see if we can do it anyway.”
The year was 2003 and to most of the therapeutic research industry, the idea of a preventative cancer vaccine was not only impossible, but it was also laughable. This despite the fact that the impossible was happening what seemed like every day. Just months earlier, scientists at the National Cancer Institute had used adoptive transfer to reduce melanoma tumors in nearly a dozen patients. And researchers at the Sloan Kettering Institute built the first effective chimeric antigen receptor (CAR) T cells, which have since been used in multiple immunotherapies to recognize and destroy cancer cells more efficiently. But it wasn’t just that cancer research breakthroughs were happening like clockwork. An analysis of published data provided plenty of reason to believe that the naysayers had it wrong, and a preventative cancer vaccine was indeed possible. So, the team set out to prove it.
Early years in preventative cancer vaccine research were filled with discovery.
From the beginning, the small team of researchers was focused on neoantigens and RNA as a source of errors, a sharp left turn from the then-popular study of self-antigens and DNA as a source of errors. A breakthrough came in that first year when a sequence of the project’s first library of RNA from mouse melanoma revealed two frameshift neoantigens (FSNs), proving the team just might be onto something. By 2005, studies revealed that both FSNs provided protection against the melanoma tumors, and that protection was on par with other disease-based vaccines, like the one for Influenza A. When the same study was applied to mouse breast cancer, the team detected that only one of the FSNs was present. That wasn’t just good news, it was a definitive moment: proof that it was possible to develop a preventative vaccine. By 2007, that good news transferred from mice to humans when the FSNs that protected mice were found in human tumors. The next year, the team discovered that FSNs elicit antibodies, a find that made it possible to search hundreds and thousands of samples for FSNs to find potential vaccine components.
Despite all this success, community support didn’t materialize.
“With a whole community against us, we had to decide whether to go on. And we did… with one sharp left turn.”
Between 2005 and 2015, grant rejections piled up, and the scientific community still wouldn’t get on board with the plan for a preventative pancancer vaccine. But hope wasn’t yet lost. In 2005, researchers from the Broad Institute of MIT and Harvard sequenced the dog genome, and found that it was remarkably like that of humans. What’s more, the many similarities made dog diseases, including multiple types of cancer, near-perfect biological analogs for diseases and cancers in humans. By the time Calviri was founded in 2015, the use of dogs to study human biology was well-accepted in the scientific community. So, the team shifted focus to creating a preventative cancer vaccine for dogs. That’s when the project’s fortunes began to turn.
Paws up for an end to cancer, and maybe other diseases, too.
In 2018, the team published its first research paper on the potential for a preventative pancancer vaccine, and the Open Philanthropy Project infused the research with a grant totaling roughly $6.4 million to support the launch of the largest canine clinical trial for cancer ever conducted. Launched in 2019, the 5-year Vaccine Against Canine Cancer Study (VACCS) successfully enrolled 800 dogs in less than three years, allowing for a fully enrolled double-blind study of the Calviri vaccine. Aside from being the largest canine cancer clinical trial ever, there’s something else unique about it: the participating dogs are not research or lab dogs. They’re healthy, well-loved pets whose pet parents voluntarily enrolled their dogs to help put an end to canine cancer, and human cancer, too. Four years in, the data being collected is already unlocking information that could change the way cancer is detected, diagnosed, and treated. Scientists have gained insights into cancer screening frequency, the need for routine imaging, and potential diagnostics for aging populations of the four-legged and two-legged variety.
But it’s the clinical data on cancer and diseases that’s really creating a buzz. During clinical trials, scientists found that the vaccine was doing two things: as expected, it’s protecting patients from cancer, but surprisingly, it’s also protecting them from non-cancer diseases.
There’s a long road ahead for a preventative cancer vaccine, but it gets shorter every day.
Importantly, an independent Data Safety Monitoring Board determined in 2021 and 2022 that the clinical trial was free from any significant adverse events. That’s important because it means researchers can move on to the next stage of investigation: efficacy. Researchers are still learning about the dog genome and how cancer forms, mutates and spreads. This makes a test of efficacy critical to the success of the vaccine, not only for veterinary use, but also for the potential of a human clinical trial. The more scientists learn about the immunology of canine cancer, the better they will understand human cancer.
And while efficacy testing for the canine preventative pancancer vaccine has a little more than one year left to go, the team isn’t waiting around. Using learnings from the current trial and previous and new research, Calviri currently is investigating potential therapeutic vaccines for hemangiosarcoma in dogs and renal medullary carcinoma in humans, and a pediatric brain cancer vaccine for neurofibromatosis in humans. And the team hasn’t forgotten about those who already have cancer or who will face a diagnosis before a vaccine to prevent it is available. Improved diagnostics for stage 1 breast and colorectal cancer, and multi-cancer ICI response and adverse events predictors are already in the development pipeline.
A vaccine injury lawyer shares his opinion: “The chronicle of Calviri’s preventative pancancer vaccine is emblematic of the tenacity of human endeavor in medical science. It’s a tale that beckons a future where the word ‘cancer’ might not invoke fear but a sense of conquerable challenge. Yet, it also casts a spotlight on the imperative for a strong legal scaffold to ensure that the pathway to such a future is paved with safety, ethics, and justice, elements integral to the practice of vaccine injury law.”
The year is 2023 and to most of the therapeutic research industry, and the world, the near-term reality of a preventative cancer vaccine has everyone on the edge of their seats, waiting to see what comes next, and when. If current research is any indication, what’s next could very well be the end of cancer and the when could be sooner than we think.
Amy Carissa Oliver
Amy Carissa Oliver is an Independent Science Researcher.
