Coley’s reasoning was that infection could stimulate the immune system to fight cancer. This idea, which was controversial during his lifetime, did not become more widely accepted by scientists until the 1950s. Today it is making efforts to create a new generation of treatments known as “cancer vaccines”, which aim to train the immune system to recognize tumors and fight their spread. Trials are now underway against cancers found everywhere from the skin and ovaries to the brain. And lungs. After half a century of frustrating stagnation, promising results are beginning to emerge.
Cancer can start in almost any cell in the body. The immune system usually tries to stop it from spreading by monitoring abnormal cells in the body. For example, white blood cells, known as T-cells, attack tumors by recognizing foreign proteins known as non-self antigens on their surfaces. So-called natural killer cells and macrophages can also identify and destroy cancer cells by detecting unfamiliar molecules they carry with them or after being tagged by antibodies.
However, if cancer cells evolve to evade the immune system, they can grow, replicate, and spread throughout the body. However, this broader maneuver is now providing oncologists with new targets for their drugs. When scientists first began sequencing the DNA of tumors in 2008, they found that cancer cells had hundreds if not thousands of mutations that distinguish them from their healthy neighbors. Some of these mutations in cellular DNA cause cancer cells to produce abnormal proteins, known as neoantigens, which can raise alarm bells to the immune system.
The idea behind cancer vaccines is to inject these nascent antigens directly into the body, thereby training the immune system to view any cancer that carries them as a foreign body, ready for eradication. Is ready.
harder than it seems
To create such a vaccine, scientists would first have to take a tumor sample, sequence its genome, and find all its genetic mutations. This information is analyzed to predict which nascent antigens are likely to elicit the strongest immune response from the body. A vaccine can then be created that will trigger the immune system to make antibodies against those specific abnormal proteins. This is done by introducing a short-lived piece of genetic information, known as RNA, which, once injected, instructs the body’s cells to produce the neoantigen. The resulting immune response will hopefully target the original tumor.
The principle is solid, but making such a specialized vaccine so quickly ready for use is a different matter. “Not many years ago, I would have said, wait, this will never be technically possible,” says Alan Melcher, a clinical scientist at the Institute of Cancer Research in London.
The fact that this is now possible within as little as six weeks – even if it comes at a cost – is in no small part due to the use of mRNA vaccines (which carry a molecule of messenger RNA) during the Covid-19 pandemic. ) has rapid growth. The vaccines used against COVID-19 produced one of the component proteins of SARS-CoV-2 in the body, which the immune system used to make antibodies. Cancer vaccines will do the same for proteins produced by tumors.
Some promising preliminary results have been published. An individual mRNA cancer vaccine developed by two US pharma firms Moderna and Merck for melanoma (a type of skin cancer), known as mRNA-4157 (V940), recently entered a Phase 2 trial in patients who Completed whose advanced tumors have been surgically removed. Three years after treatment, the risk of cancer recurrence or death was almost halved. This is a promising finding for the Phase 2 trials, but a definitive answer on the vaccine’s usefulness will have to wait for the results of later phase trials.
Many people think that such vaccines may be most effective in combination with other immunotherapies – which work in different ways to boost or control the immune system’s response to cancer. Sarah Danson, an expert in early-stage cancer research at Britain’s National Institute for Health and Care Research, explains, “We are giving many cancer vaccines with immunotherapy to improve the immune system.” In fact, mRNA-4157 (V940) was given along with the current standard of care, which includes another form of immunotherapy, a drug called Keytruda (pembrolizumab).
Moderna and Merck announced in June 2024 that they had tested mRNA-4157 (V940) in patients with non-small cell lung cancer, renal cell carcinoma (a type of kidney cancer), and urothelial carcinoma (a cancer of the urinary lining). Further study has been started. ) and cutaneous squamous cell cancer (a type of skin cancer) to test its effectiveness against various tumors. BioNTech and Genentech are also jointly evaluating personalized vaccines in different types of cancer. There is already a hint in the data that their vaccine, known as Autogene Sevumaran, may reduce the risk of pancreatic cancer after surgery.
Glioblastoma – the most common brain cancer, and for which no useful treatment exists – is also being targeted. In work by academics at the University of Florida, an mRNA-based cancer vaccine tested on only four people produced evidence that the vaccine triggered a strong immune response to tumors. Trials on dogs with brain tumors have also been promising: they lived an average of 139 days after treatment, whereas those without it would normally be expected to live 30–60 days. These results in humans and dogs also show that a personalized vaccine could trigger an immune response in “cold” tumors – ones that the immune system doesn’t normally recognize or fight.
The hope is that cancer vaccines will advance to the point where they will reduce the need for more aggressive treatments such as chemotherapy or surgery. For Dr. Danson, it’s also possible that therapeutic cancer vaccines could one day be used for prevention — vaccines against neoantigens commonly found in various cancers, given to people most likely to develop them. There is more danger. In October 2024, scientists at the University of Oxford were awarded funding to create a preventive ovarian cancer vaccine aimed at identifying and attacking the early stages of this cancer.
It won’t all be plain sailing. Creating personalized cancer vaccines is complex and expensive. Creating off-the-shelf cancer vaccines, such as an ovarian-cancer vaccine, could help. Another example – which goes even further – is BioNTech’s mRNA vaccine candidate for non-small cell lung cancer. Then, this vaccine presents the immune system with common tumor markers found in different types of cancer. This work is still in preliminary safety tests.
Important scientific questions also remain unanswered. For one thing, says Elad Sharon, MD, clinical and translational director of the Dana-Farber Cancer Institute in Boston, it’s not clear why the immune system would ignore a nascent antigen if it’s produced by a tumor, but that’s when it will. She will leap into action. Delivered by vaccine. Pharma companies also need to rigorously evaluate their neoantigen-selection techniques to ensure the best candidates are selected.
time to shine
More than a century after perfecting his experimental treatments, Coley’s instincts have been proven correct. But how effective modern vaccine candidates will be is unknown. A study published in 2009 assessed developments in this field and wondered whether that would be the year of the cancer vaccine. It was not. However, 2025 may be a different story.
