The idea of a universal cancer vaccine remains elusive, but the use of vaccines to treat cancer is showing increasing promise. Recent research presented at international conferences is fueling optimism about therapeutic vaccines and their potential to halt disease progression or prevent recurrence.
In June 2025, leading oncologists from around the world will gather in Chicago for the annual meeting of the American Society of Clinical Oncology (ASCO). This year, vaccines are taking center stage in discussions about cancer treatment.
It’s important to note that the focus is on therapeutic vaccines, not preventative vaccines. Unlike vaccines that prevent illness, such as those for the flu or rubella, therapeutic vaccines are designed to prevent a disease from progressing or returning. This distinction is crucial as researchers explore recent ways to harness the power of the immune system to fight existing cancers.
Two French biotech companies, Transgene and OSE Immunotherapeutics, are at the forefront of this research. At the ASCO meeting, they will present preliminary, yet promising, results. Their function demonstrates the possibility of inducing a durable immune response in patients already battling cancers of the head and neck (not related to HPV), as well as HPV-related cancers for Transgene, and pancreatic cancer for OSE Immunotherapeutics.
While these studies don’t yet prove that these vaccines will extend patients’ lives, the results are strong enough to justify continued research and reinvigorate a dream researchers have pursued for decades.
A Vaccine to Teach Our Immune System to Recognize Cancer
The foundation for this work was laid in the 1990s, when cancer treatment primarily relied on aggressive methods like chemotherapy and radiation therapy. The current approach, focused on more targeted therapies like immunotherapies, aims to boost the body’s own immune defenses against cancer. Early skepticism centered on the question of whether our immune systems could attack cells that originated within our own bodies.
The principle behind our immune system is straightforward: it’s “educated” to attack anything foreign to the body. All cells display “identification cards” on their surface – small fragments of the macromolecules that compose them, particularly proteins – called antigens.
Tumors: Healthy Cells with Falsified IDs
Our immune system, particularly lymphocytes, regularly patrols the body, checking these IDs. Healthy cells are allowed to function normally, but if a cell is infected with a virus, it displays viral antigens, signaling to the lymphocytes that the ID is “falsified.” This triggers the destruction of the compromised cell.
TO EXPLORE: Sometimes a picture is worth a thousand words. To better understand how cancer cells evade our immune system, browse our comic book on The Elusive Gang of K.
Can cancer cells, originating from our own bodies, likewise present a “falsified” ID? In the 1990s, the team led by Thierry Boon answered this question with a resounding yes. They discovered that tumor cells not only present a falsified ID but also trigger an immune response against them.
“Tumor cells become cancerous due to mutations that give them the ability to proliferate rapidly and survive in unfavorable conditions. These mutations also make them different from normal cells. Previously considered a negative thing by oncologists, these mutations appeared to immunologists as a formidable opportunity,” explained Pr Éric Tartour, head of the biological immunology department at European Hospital Georges-Pompidou and Necker Hospital.
Cancer Vaccines: A Path More Than 20 Years in the Making
This discovery marked a paradigm shift: to fight tumors, the immune system could become a powerful ally if helped to identify the enemy. This is precisely the role of the vaccination approach – to present tumor antigens so that the immune system can track and eliminate any cell displaying them.
The first trials began in the 2000s, with prostate cancer and melanoma emerging as promising candidates, as researchers had already identified antigens expressed by these tumors. The chosen vaccination approach was complex, relying on the use of dendritic cells, which specialize in presenting antigens. These cells are extracted from the patient, genetically modified in the laboratory to present a tumor antigen, and then re-injected into the patient.
“This process was extremely laborious. So, even though the results were promising, the research was abandoned,” explained Pr Palma Rocchi, director of the Inserm RNAnoTher laboratory. The antigens used in these vaccines also had a major drawback: they weren’t specific to the tumor, potentially causing collateral damage to healthy tissues that also expressed them. Vaccinotherapy stalled, but not for long.
DNA Sequencing: A Revolution That Revived Cancer Vaccines
“Everything was relaunched in 2005 with the advent of next-generation DNA sequencing, or NGS,” recounted Dr Tartour. This revolutionary method reduced the time to sequence a genome from a decade to just a few days. The team led by Dr. Steven Rosenberg was among the first to seize its potential in oncology, using it to compare the DNA of a patient’s tumor to that of their healthy tissues and identify mutations specific to the cancer.
Despite this advance, a significant challenge remained: some mutations affect parts of the DNA that don’t code for proteins, and the mutation may not be located in the fragment of the protein that will be presented on the tumor surface. How can we know in advance which DNA mutations will yield mutated proteins, and which fragments will be exposed to the immune system?
Once again, the rise of a new technology would change the game: artificial intelligence (AI). “Tumors contain an enormous number of mutations. Thanks to algorithms, One can determine which mutations are most likely to trigger an immune response,” reported Pr Tartour.
ALSO SEE: To learn more about the role of AI in oncology, watch the replay of our webinar with Pr Sarah Watson, an oncologist at the Institut Curie and AI specialist.
The Prospect of Tailored Cancer Vaccines
From there, a paradigm shift occurred: to fight tumors, the immune system can become a powerful ally if helped to identify the enemy. This is precisely the role of the vaccination approach: to present antigens to the immune system so it can track and eliminate any cell displaying them.
Transgene, inspired by this approach, launched the development of individualized vaccines about seven years ago. “These developments opened up a new path,” confirmed Alessandro Riva, CEO of Transgene.
To maximize its chances of success, the French biotech partnered with NEC, a Japanese company specializing in AI. “Today, we can, from a fragment of an operative piece taken from a patient, sequence the DNA of healthy and tumor cells that compose it. We then send the sequences to NEC, which provides us with a long list of neoantigens [antigens specifically expressed by the tumor, ed.],” detailed Dr. Riva. Why so many? “Because even with the best algorithms, only one in four selected neoantigens will induce an immune response,” explained Pr Tartour.
Transgene isn’t the only company venturing into this area. Leveraging their expertise gained during the COVID-19 pandemic, Moderna and BioNTech have also joined the effort. In 2023, both laboratories presented initial results of their individualized vaccines – Moderna in melanoma treatment, and BioNTech in pancreatic cancer. Like those presented by Transgene, these results are preliminary but offer hope.
Several Cancer Vaccines in the Pipeline
Moderna’s V940 vaccine, for example, reduced the risk of recurrence and death by 44%. This result earned it Breakthrough Therapy Designation in the United States and PRIority MEdicines Designation in Europe, statuses granted by health authorities to accelerate the development and review of innovative drugs.
“Phase 3 trials will be needed, with a larger scope, to validate its efficacy. But we have high hopes for these results, particularly in melanoma, following the positive results of the phase 2 trial. If they are positive, we will soon have a new class of drugs,” emphasized Pr Tartour.
And if they are negative? That would be a setback: “Melanoma is a cancer that responds well to treatments such as checkpoint inhibitor immunotherapies, which, like vaccines, rely on our immune system. If vaccines don’t work in melanoma, there’s little chance they’ll work in other cancers [those that respond less well to ‘immunological’ treatments, ed.],” worried Pr Caroline Robert, head of the dermatology department at Gustave-Roussy and investigator of the study.
Against Cancer, Vaccines Must Be Administered at the Right Time
Beyond technological advances, the success of these vaccines also depends on timing. “In other trials, attempts were made to use them against metastatic cancers, but researchers failed,” observed Pr Aurélien Marabelle, director of the translational research laboratory in immunotherapy at Gustave-Roussy. “There are two main reasons for this. First, because the tumor is too large compared to the number of lymphocytes generated by the vaccination. Second, because over time the tumor develops mechanisms that inhibit the action of the immune system.”
“The vaccine stimulates our immune system outside the tumor,” added Dr Cindy Neuzillet, a digestive oncologist at the Institut Curie. Facing a large and dense tumor like pancreatic cancer is like sending soldiers into a jungle: they will have difficulty penetrating it.”
Current approaches seek to administer the vaccine earlier, when the tumor is operable. The vaccination is then used as adjuvant treatment, after surgery, to limit the risk of recurrence. This also gives laboratories time to produce the vaccine. Today, from genetic analysis of the tumor to production of the individualized vaccine, it still takes several months. “A year and a half ago, it took us six to seven months,” noted Dr. Riva. “Currently, we are able to produce an individualized vaccine in three months and hope to reach two and a half months, or even two months soon.”
Ready-to-Use Vaccines Against Aggressive Cancers
A timeframe acceptable in the context of head and neck cancers, on which Transgene has focused its individualized TG4050 vaccine. But this isn’t the case for other, more aggressive cancers. “In pancreatic cancer, by the time we prepare the vaccine, 15 to 20% of patients will see their disease recur despite surgery, even if they receive adjuvant chemotherapy,” related Dr. Neuzillet. These patients will therefore not be able to benefit from this type of vaccine.”
“Currently, we are able to produce an individualized vaccine in three months and we hope to reach two and a half months, or even two months soon” – Dr Alessandro Riva
The solution? Ready-to-use vaccines, or “off the shelf” vaccines. “This requires finding shared mutations by a majority of patients, which is quite rare,” specified Dr Tartour. But not impossible. The Kras gene, for example, is mutated in about a quarter of small cell lung cancers, in about half of colorectal cancers, and in the vast majority of pancreatic cancers. Vaccines targeting these mutations are in early stages of clinical trials. Not to mention virally-induced cancers, such as those related to HPV. In these specific cases, the antigens to target for the vaccine are readily available – simply targeting those of the virus, as with any classic antiviral vaccine.
This is the approach Transgene has taken with its TG4001 vaccine. “We chose to prioritize the individualized approach over the ready-to-use approach, even though we believe they are complementary. Ready-to-use vaccines have the advantage of being immediately available, but they won’t address all situations. Individualized vaccines, thanks to their high specificity, have that potential,” concluded its CEO. A dual strategy that researchers hope will be successful.
A BARRIER AGAINST IMMORTALITY
Each cell division leads to the erosion of the ends of our chromosomes, the telomeres. When they become too short, the cell dies. Not tumor cells, which are able to activate an enzyme – telomerase – allowing them to regenerate their telomeres. It is against this mechanism that confers immortality to tumor cells that the team of Pr Olivier Adotevi, from the CHU of Besançon, is currently developing the vaccine UCPVax. Its good tolerance and its ability to trigger an immune response have already been confirmed, it is now the subject of a clinical trial to determine its efficacy in lung cancer, in association with an anti-PDL1 immunotherapy, in second-line treatment. These works are carried out with the support of the Arc Foundation.
This article was published with the support of the Arc Foundation.
Find this article in Rose magazine n°29, page 90.
Chief Editor of Rose magazine’s website. Holding a doctorate in biology, Emilie worked for 10 years in the field of biotechnology patents before transitioning to journalism. She joined the editorial staff of Rose magazine in 2018. Her specialty: popularizing complex scientific subjects to make them accessible to the widest possible audience.
