New frontiers in nipping cancer in the bud

Just a few generations ago, childhood illnesses like measles and diphtheria ran rampant, and Americans were dying from infectious diseases like these and even seasonal flu at alarmingly high rates. Since the advent of robust and widespread vaccines against many of these illnesses, chronic conditions like cancer now cause the most mortality nationwide. What if vaccines against cancer could have the same success?

The idea of vaccinating against cancer isn’t new—just challenging, because cancerous tumors have many tricks to avoid being seen as a target for the immune system. But today, after more than 50 years of federally funded research into the architecture of immunity, scientists have the clearest picture to date of how the immune system can fight off cancer before it takes root.

The idea behind cancer interception is familiar to anyone who has experience with weeding a garden: It’s easier and more effective to uproot a tiny seedling when an invasive species first appears, than to eradicate an established patch of a noxious weed.

So, too, researchers hope that the idea of cancer interception will transform how precancerous growths can be nipped in the bud before they advance into diagnosable tumors. It’s different than cancer prevention strategies, such as quitting smoking, which can stop cancer from even beginning to form. Instead, cancer interception is a model of intervening at the very earliest stages as abnormal cells begin down a path that can later become cancer.

This spring, Penn Medicine scientists showed for the first time that a medical intervention could stop growth of pre-cancerous lesions in the pancreas at such early stages before they develop into pancreatic cancer, in a mouse model.

Complementing that progress, work on developing new cancer interception vaccines is now accelerating with the goal of stopping cancer before it starts by harnessing the power of the immune system.

How do we strengthen the immune system to stop cancer before it starts?

The Basser Cancer Interception Institute is supporting a five-year, $5 million grant in immune interception that builds on this earlier work and on Penn Medicine’s strengths in immune health and mRNA vaccines.

It creates an internal platform for fast-tracking basic science research to preclinical screening to, eventually, a broader array of promising personalized cancer vaccines for clinical trials.

“It's really ambitious to say out loud, ‘We want to intercept cancer,’” said the leader of this immune initiative Christopher Hunter, PhD, the Mindy Halikman Heyer Distinguished Professor of Pathobiology at the University of Pennsylvania School of Veterinary Medicine. “It’s a gutsy approach.”

It’s also a timely approach, as cancer vaccines seem poised to grow even in a challenging funding landscape: A new public-private partnership between the National Cancer Institute and the Foundation for the National Institutes of Health is proposing a plan to invest $200 million in cancer vaccine research. Robert Vonderheide, MD, DPhil, director of the Abramson Cancer Center, serves as a member of the Cancer Vaccines Initiative Design Phase Committee, a national group of academic, federal, biotech and industry scientists who advise on the partnership and its plans.

The Basser Cancer Interception Institute’s immune-interception initiative will double-down on cancer vaccine efforts already underway at Penn, said Susan Domchek, MD, executive director of the Basser Center for BRCA. “We’re leveraging the immense resources of Penn Medicine to develop an optimal approach,” she said, “so we can test systematically and rapidly and bring [vaccines] to patients.”

Building on key strengths

Everyone’s bodies contain pre-malignant cells that have the potential to become cancer, Hunter said. Usually, the immune system “prunes” those cells, stopping cancer before it starts. When that process breaks down, or the pre-malignant cells evade immune system detection, cancer develops. “Our immune system is functioning all the time, but sometimes it fails and the cancer escapes,” he said. “We should be able to use a vaccine to bolster [the immune system] therapeutically, to educate it to be more effective at getting rid of these pre-cancerous cells.”

Penn Medicine has made an institutional commitment to immunology and immune health research and has a track record of pioneering new therapies that use the immune system as treatment. A key example is CAR T cell therapy, which programs patients’ own immune cells to fight their cancer.

Another, related strength is mRNA technology, which has been honed over three decades of research at the Perelman School of Medicine. Drew Weissman, MD, PhD, the Roberts Family Professor in Vaccine Research, won the Nobel Prize with Katalin Karikó, PhD, in 2023 for discovering mRNA technology that led to highly effective COVID-19 vaccines. Weissman now leads the Institute for RNA Innovation at Penn, which is an epicenter of continued discovery to develop and test new mRNA-based vaccines and therapies for a wide range of diseases.  “It doesn’t take us six months to make the RNA; we can do it in a couple of weeks,” he said. “We’ve got the ability to design experiments quickly and get great results.”

Although there are other vaccine formulations being developed, mRNA vaccine technology offers more speed, flexibility, precision, scalability, and adaptability than traditional modes of vaccine development. “This is a platform that makes everything easier to play with as an immunologist,” Hunter said. “We’re using the platform to make the vaccines better.”

Interception vaccines that are proven safe and effective could provide a new treatment option for people with a genetic predisposition to cancer, just as preventive mastectomy currently is for people with a BRCA genetic mutation.

“It becomes something else in the physician’s armory,” Hunter said.

As cancer screening continues to improve—Weissman is working with a company developing a screening test that identifies Stage 0 colon cancer, for instance—the opportunities for interception broaden to offer future vaccines to help even more people avoid getting cancer in the first place.

It’s an ambitious vision, where each methodical step is essential—but methodical doesn’t have to mean slow.

“We’re getting all these pieces into place,” Domchek said, “aiming to get to an inflection point where you can move things along more quickly.”