How Cancer Vaccines Could Bring a New Future

In the closing months of 2023, I was saddened to learn that cancer had claimed another member of our Stanford Medicine community. Aruna Gambhir was an accomplished executive leader, with a deep expertise in software development and a delightful ability to connect with people. She passed just three years after her husband Sam Gambhir, MD, PhD, a brilliant physician scientist who served as chair of our radiology department; and eight years after her teenaged son Milan. Both of them also died of cancer.

Their story is unique in its details, and yet familiar in its arc. Each year, nearly 2 million people in the U.S. receive a new cancer diagnosis, and cancer has been among the top two leading causes of death for 75 years. In that time, much has changed about how we understand the disease and what we can do to treat it, prevent it, and even cure it. Today, scientists are making significant headway with new approaches that train the body’s immune system to eradicate its invaders. One of the most promising areas of immunotherapy in oncology would have seemed unlikely just ten years ago: cancer vaccines.

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Different from traditional vaccines

Traditional vaccines are preventative, protecting from infection by injecting a dead or weakened version of a virus into the body to help the immune system identify and destroy it. For cancer, these types of vaccines protect against viruses known to cause certain cancers, including the human papillomavirus or HPV and the hepatitis B virus, associated with cervical and liver cancers respectively. Another type of vaccine helps the body fight cancer cells that have already emerged. Broadly, they work in the same way as traditional vaccines: by introducing a harmless molecule into the body to program the immune system for attack.

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Using mRNA vaccine technology against cancer

The technology underlying some of the more prominent cancer vaccines is familiar to many. The mRNA platform — recognized last year as a Nobel Prize-winning innovation — was being developed as a cancer therapeutic years before COVID-19 urgently brought this technology into the limelight in vaccines rapidly developed to help to control this virus around the world. These types of vaccines work by using messenger RNA— known as mRNA — to transport into the body the genetic blueprint for a protein found on a disease cell. This information triggers the body to produce harmless versions of the disease proteins. Immune cells then learn to recognize these proteins on cancer cells and attack the malignant cells.

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Promising results in clinical trials

An advantage to this platform is that the genetic instructions can be reprogrammed with relative ease. For COVID-19, this has helped scientists quickly create booster shots targeted for emerging variants. For cancer, it provides a way to develop a personalized cancer vaccine based on the unique genetic makeup of an individual’s tumor cells. Several such vaccines have grabbed headlines in the past year, showing positive results when used in combination with other therapies. Last spring, a small clinical trial of an mRNA vaccine against pancreatic cancer — one of the most deadly and aggressive cancers — found that the vaccine induced an immune response in half of the patients and that they showed no relapse in their cancer during the study. Last month, makers of an mRNA vaccine against deadly skin cancers reported significant results from their clinical trial, with participants receiving the vaccine 49% less likely to die or have a recurrence of their cancer. To be sure, these are still very preliminary results, but the potential here appears significant. Investigation of these mRNA vaccines continue, along with others targeting colorectal cancer, head and neck cancer, and other types.

Technologies for broader application

Scientists also are exploring technologies that would allow for cancer vaccines that don’t require personalization. In this approach, rather than training immune cells to attack specific tumors, a vaccine could be engineered to reactivate biological signals that cancer cells are known to suppress, which effectively make them invisible to our immune systems. Reawakening these signals could aid the immune system to ‘see’ cancerous cells and destroy them.

?At Stanford Medicine, the laboratory led by Ronald Levy, MD, devised such a method, whereby very small amounts of two immune-stimulating agents were injected directly into a tumor site. The treatment worked extremely well on mice, and is now being tested in a clinical trial for patients with low-grade lymphoma. As that trial continues, Levy, who is the Robert K. and Helen K. Summy Professor in the School of Medicine, and his colleagues at Stanford are building on the original technology. Jennifer Cochran, PhD, the Shriram Chair of the Department of Bioengineering, and Carolyn Bertozzi, PhD, Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences and professor of chemistry, led the development of a new synthetic molecule that both targets a tumor and triggers immune activation in the body. An advantage of this approach is that the molecule can be administered intravenously, making its way to the cancer cells through the bloodstream, rather than being injected directly into the tumor. This emerging therapy also has shown promising results in laboratory mice.

Optimism for the future

All told, we’re on the threshold of a new age in cancer therapy. Decades of rigorous research have brought an increasingly sophisticated understanding of how cancer cells invade and conquer our bodies. Building on this store of knowledge, scientists around the world have gained momentum in developing novel ways to activate our immune systems in an effective defense. This year, I expect we will hear more about the progress of cancer vaccines and what they can do to lift our ability to treat this disease. As these and other technologies continue to progress, a new future comes into focus —?one where cancer is no longer the killer that we’ve known it to be.

These resources provide more information about mRNA, vaccine development, and cancer research.

Special?delivery: mRNA moves past COVID-19? (Stanford Medicine Magazine). This article provides an in-depth explanation of mRNA technology, how it powers COVID-19 vaccines, and potential applications for vaccines against other diseases.

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And?yet,?there’s hope: A family devastated by cancer plants seeds to vanquish the disease? (Stanford Medicine Magazine). The Gambhir family’s battle with cancer was unusual and devasting; but their determination to make a difference for future generations is nothing short of inspiring. This beautiful piece chronicles their courageous journey and scientific legacy.

The next big advance in cancer treatment could be a vaccine (Associated Press). This article provides more detail about the science behind cancer vaccines and their promise to boost the immune system and destroy tumors. Disease areas of interest for this approach include breast, lung, ovarian, skin, and pancreatic cancer.

Is AI the Cancer-Fighting Tool We've been Waiting For? (Newsweek). This article focuses on artificial intelligence and its potential to advance cancer research. It discusses using AI to design anti-cancer drugs and identify patient populations most likely to respond to treatments.

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