The Cure for Cancer?

Earlier this year, two small cancer research companies merged: one public, the other private. The public company, Kintara had just published negative results in a clinical trial, which predictably turned the pre-revenue biotech into a financial zombie, unable to raise capital. It was a shame because Kintara had other promising programs … but this isn’t their story. Rather, it’s the tale of the private company, now called TuHura Biosciences, and the brilliant idea that their founder plucked from ancient history to create what may actually be the cure for cancer.

Do I have your attention?

The full story requires a quick journey through the history of cancer treatment, beginning nearly five thousand years ago in the Egyptian court of the very first physician … ever. I’m speaking, of course, of Imhotep, who lived so long ago that, today, we’re closer to Julius Caesar than he was! Amazingly, surviving papyrus writings describe Imhotep inducing infections in cancer patients to activate their immune systems to treat tumors. All signs are … it worked!

Fast forwarding some 3,500 years, we meet Peregrine, an Italian priest. Church records (admittedly, not exactly electronic medical charts) indicate that Peregrine suffered with an aggressive tumor in his leg, which had burst through his skin. In extreme pain, Peregrine faced amputation as his only option. Legend has it Peregrine prayed fervently, fell into a deep dream state in which Jesus touched his leg, and woke to his leg healed. The Catholic Church proclaimed it miraculous and promptly canonized him Saint Peregrine. Medical historians, being a bit more skeptical, speculate that an infection (a common complication of tumors breaching the skin) triggered an immune-based tumor regression.

Launching forward several hundred years, we enter New York Hospital in 1891 to find a young William Coley, presented with a teen with bone cancer (osteosarcoma). Her name was Elizabeth Dashiell, a close friend of a young John D. Rockefeller, Jr. Coley was, unfortunately, tasked with the grisly job of amputating her arm at the elbow. Months after the surgery, however, he was devastated to find her dying from tumors growing throughout her body. His treatment had failed.

After Elizabeth’s death, Coley began a quest, motivated by Rockefeller, who ultimately endowed the cancer research leading Rockefeller University, to find an osteosarcoma survivor. Nearly a year later, Coley found forty-year-old records of a German immigrant who had presented with a tumor in his jaw. After multiple failed resection surgeries, the wound had become impossible to close, leading to multiple infections. With each bout of “fevers,” the tumor receded until, like Saint Peregrine, he fully recovered.

In the 1890s humoral and cellular immune mechanisms had yet to be described. Still, Coley was aware of Jenner’s famous cowpox inoculations against smallpox and knew infections of one type could teach the immune system to fight another. Expanding on this idea, Coley reasoned that bacterial infections might activate the immune system to attack tumors. Sound familiar? The rules for clinical trials were significantly less rigid back in 1891, when Coley began infecting cancer patients with streptococcus pyogenes. According to legend, his first patient was miraculously cured, however, several subsequent patients suffered lethal septic responses.

Undeterred, Coley modified his treatment, heat-killing the bacteria before injecting tumors. His brew, dubbed Coley’s Toxin because it retained its immune-triggering “toxicity,” proved remarkably successful. In fact, within a few years, it became the standard of care for many cancers. However, without centralized manufacturing, the therapy varied widely, leading to unreliable outcomes. For the want of consistent production, the proverbial door was left open, and Coley’s Toxin was sidelined a generation later by radiation and chemotherapy agents.

With one final jump, we land in the 1990s to meet Mike Lawman, a brilliant researcher with exotic origins growing up in Rhodesia (now Zimbabwe), transplanted to the University of Florida. Always curious about past clinical observations, Lawman leaned into Coley’s story and started thinking. Armed with twentieth-century biological advances, Lawman imagined ways to reliably trigger the body’s infection response to turn it on tumors. What Coley, and Imhotep before him, had attempted was the equivalent of dumping a tanker of gasoline onto a car, hoping some would leak into the tank. Lawman knew there was a better way.

The better way started with a protein, derived from a rare strain of good ole streptococcus pyogenes, that had been sequenced by Lawman’s colleague. Like many bacterial proteins, Emm55, was highly immunogenic (i.e., triggers immune response), but Emm55 had a rare quality for bacterial proteins; it includes a transmembrane sequence allowing it to be positioned on the surfaces of human cells. Lawman’s idea was to inject the gene for Emm55 into tumor cells to trick them into expressing the protein, which would then serve as the immune equivalent of a flight recorder beacon for immune cells.

Lawman’s idea worked. By transfecting cancer cells harvested from animals with cancer (i.e., exposing them to the Emm55 gene in a test tube) and reinfusing them into the animals, Lawman caused tumors to shrivel up within days. It even caused similar tumors in other areas of the body to shrink and disappear (called the abscopal effect). And when trying to regrow the cancers in the same animals, he found they had become immune.

Developing cancer therapies is an expensive business. Fortunately, Lawman’s company caught the eye of a billionaire physician, who deemed their therapy worthy, and ultimately brought in the proven biotech CEO, and brilliant oncologist in his own right, Dr. James Bianco. (For a few years, prior to Dr. Bianco joining TuHura, I was honored to serve on the Board of Directors.)

TuHura is currently the sponsor of one of the broadest cancer studies (called a basket trial) ever approved by the FDA. Even prior to their recent merger with Kintara, they were partnered with the pharmaceutical giant, Merck, to study their Emm55-based vaccine (now called IFx) in combination with the blockbuster immune-booster, Keytruda.

Will IFx live up to the expectations of those of us who have been following its progress through the FDA? If having research partners, like the members of the Karolinska Institute (the folks who hand out the Nobel Prizes) is any indication, I think their future is bright. Today, close to five thousand years after Imhotep first envisioned harnessing the power of the body’s infection response to treat cancer, a thousand years since the miracle of Saint Peregrine, and a century from the introduction of Coley’s Toxin, we stand at the figurative precipice of a new world, with optimism that we will soon say, “Yes, we just cured cancer!”

JP Errico is a highly accomplished scientist with a diverse range of expertise as an executive, entrepreneur, and inventor. He is an expert on the Autonomic Nervous System. He is the Founder of ElectroCore, where he pioneered a non-invasive Vagus Nerve stimulator. JP has been credited as an inventor on over 250 issued US patents. He went to MIT for undergrad and holds graduate degrees in both law and mechanical/materials engineering from Duke University.