BioNTech is the second major vaccine manufacturer to start tests for a lung cancer vaccine. Moderna already has the most fatal cancer in its sights as well. “We can’t celebrate just yet, but this race is good news in itself,” says pulmonologist Karim Vermaelen (UZ Gent).
BARBARA DEBUSSCHERE, August 23, 2024, 6:57 PM
Currently, lung cancer patients in seven countries are receiving ‘BNT 116.’ This is an mRNA vaccine from the company BioNTech, a technique and company that became world-famous during the COVID-19 pandemic.
The couple who founded BioNTech, scientists Ugur Sahin and Özlem Türeci, did so to tackle cancers. Because they had already made significant progress with the mRNA vaccination technique against cancer by 2020, they were able to quickly provide the world with a COVID-19 vaccine. And thanks to the money and expertise gained during the pandemic, BioNTech can now intensify its search for cancer vaccines.
With BNT 116, the company hopes to save many lives. Lung cancer kills about 1.8 million people each year, making it the deadliest cancer in the world. The same is true in our country, where lung cancer is also the second most common cancer. Moreover, more and more Belgians are being affected by it.
Doctors, patients, and their families are eagerly awaiting the promised arrival of lung cancer vaccines. “We’ve been searching for cancer vaccines for decades, but only now do we seem to be on the right path,” says pulmonologist Karim Vermaelen, who is working on a lung cancer vaccine at UZ Gent.
In ‘Phase 1 trials,’ which examine whether the vaccine is safe, BioNTech’s vaccine has recently been administered to about 130 lung cancer patients in seven countries (the U.S., U.K., Germany, Hungary, Poland, Spain, and Turkey). BNT 116 is designed to target non-small cell lung cancer, the most common form of lung cancer.
ANTIBODIES
Cancer vaccines do not work preventively, but the technology is essentially the same as that in the most efficient COVID-19 vaccines. These contain building instructions for the spike protein of the virus, teaching our immune system to produce antibodies against it.
In mRNA vaccines against cancer, the mRNA or ‘messenger RNA’ molecule provides precise instructions for producing antigens. These are proteins produced by the tumor, which make the tumor recognizable. By administering these tumor markers via the vaccine, the immune system is trained to attack and kill cells with these tumor markers.
The potential benefit is that the immune system leaves healthy cells alone, a significant advantage compared to chemotherapy.
How does an mRNA cancer vaccine work?
- Genetic instructions (mRNA) to produce antigens that are also produced by cancer cells
- mRNA is picked up by immune cells or muscle cells, which ‘read’ the code and produce the cancer-specific antigens.
- Antigen-presenting cells (APCs) are triggered by the mRNA or an injected supplement to pick up the antigens.
- APCs activate the immune system by processing the antigens and presenting them to T-cells.
- T-cells attack cancer cells that produce the same antigens.
However, for our immune system, cancers are tougher to deal with than viruses. “Many cancer cells wrap themselves in a shield of connective tissue, preventing immune cells from reaching them. Also, not all tumors have the same markers, making it difficult for the immune system to recognize them,” explains Evelien Smits. She leads research on cancer vaccines at the Center for Cell Therapy and Regenerative Medicine (CCRG) at UZA and UAntwerpen.
This is why the mRNA vaccines in development against cancers like brain, breast, skin, pleural, and lung cancer are more complex than ‘universal’ vaccines against flu or COVID-19. “For example, BNT 116 uses six different markers, which is less straightforward than targeting one spike protein, as in COVID-19 vaccines,” explains Vermaelen.
GENETIC CODE
Even more complex are the personalized mRNA vaccines. “Researchers first analyze the tumor markers of the individual patient, select several, and then incorporate the genetic code to produce those markers into the vaccine tailored to that patient,” Smits clarifies. BioNTech and competitor Moderna also have such a lung cancer vaccine in the pipeline.
Moderna, together with Merck, provided the first proof last year that cancer vaccines can work. The companies published excellent results from phase 3 trials (the final research phase) with a vaccine against skin cancer. After three years, the risk of relapse in vaccinated individuals was almost half that of patients who only received the standard treatment.
Moderna is also further along with a lung cancer vaccine. “They are already in phase three, which means there are signs of effectiveness,” says Smits. “Türeci and Sahin have stated that they will be able to bring cancer vaccines to market by 2030. But because Moderna is also involved, this might happen even sooner.”
Vermaelen: “We can’t celebrate just yet because these are still test phases, and a major trial of a lung cancer vaccine from GSK has failed in the past. But this race is good news, and we are now targeting the right method, formulation, and patient population. The mRNA technique is making a big difference. We also now know that we cannot use these kinds of vaccines alone. They will be used in combination with existing immunotherapy.”
That is medication that makes the immune system extra active. “This is already part of the standard treatment for lung cancer, and in some patients, the results are positive, but many others respond insufficiently,” says Smits. “We expect that combining it with a vaccine that also shows the immune system which cells to attack will work much better.”
Specialists also expect that mRNA vaccines against lung cancer can prevent relapse. “This would also be a major step forward because currently, preventing relapse in lung cancer is difficult,” Vermaelen concludes.
**A photo of a patient with lung cancer. Image by Getty Images/Science Photo Library