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Vaccines - a new era in the fight against cancer
Health

Vaccines - a new era in the fight against cancer

Messenger RNA technology (a single-stranded molecule that tells your DNA to make proteins to build immunity) is being researched to provide immunity against melanoma

Fermín Apezteguia

Madrid

Friday, 19 April 2024, 17:28

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The appearance 17 years ago of the first, and so far the only, cancer vaccine - cervical cancer - closed the door on any future research and development to create new immunisation treatments for other tumour-based diseases.

Scientists pointed out the fact that cervical cancer was an exception to the norm for most cancers in that this particular disease is caused by a virus, human papillomavirus (HPV). All other cancers, of which there are over 200, each one different, are linked to different biological processes related, fundamentally, to ageing.

Taking a vaccine-based approach to the rest seemed to be the wrong toolset - that is, until Covid reared its head and the unforeseen development of a vaccine changed everything, re-opening this line of enquiry.

Messenger RNA technology (a single-stranded molecule that tells your DNA to make proteins to build immunity) is being researched to provide immunity against melanoma.

Results are promising and it is expected that these will favour further development of vaccines to treat the stubborn, deadly cancers in such as the lungs, breast and liver. The prototype vaccine being tested has changed everything.

"It has breathed new life into the field of cancer vaccines," says oncologist Eva Muñoz Couselo, member of the board of directors of the Spanish Society of Medical Oncology (SEOM).

"They have truly opened the door to personalised medicine in cancer, to being able to treat each patient based on their tumour and their immune system," she adds.

Across Spain hospitals treat around 7,500 cases of melanoma every year, and it is a disease on the increase. Its appearance is mostly driven by exposure to ultraviolet radiation from the sun, but sufferers can also have a genetic predisposition to the condition and people are more susceptible if they have a history of severe and repeated bouts of sunburn.

Surprisingly, 80% of melanomas occur on apparently healthy skin and only 20% – one in five cases, a substantial figure nonetheless – is due to a previous skin lesion, such as a mole, which mutates and turns malignant.

The objective of this vaccine, according to Muñoz Couselo, is to ensure that the immune system generates an effective response to the tumour's antigens. Right there the scientists found the answer to the question that was baffling them: why do all these promising prototypes, without exception, fail?

Breaking the barrier

The answer lay in the fact that the substances used to generate an immune system response were simply not strong enough. Cancer, as researchers have discovered throughout history, always ended up defeating the antigens introduced by varying treatments. But that barrier has finally been overcome. This has been made possible by advances in the development of vaccines through genetic sequencing, a technology that allows us to fully understand and decipher the genetic code of living beings.

Next-generation sequencing (NGS) provides the possibility of identifying tumour-specific antigens (the scientific term is neoantigens). These are, as Muñoz Couselo explains, a new protein that forms on cancer cells when certain mutations (autoantigens) occur in the tumour's DNA.

They help the body to make an immune response against those specific cancer cells. They constitute the "ideal target for the development of therapeutic vaccines against cancer", such as the one that has been developed against melanoma.

Therapeutic means that it is not designed to prevent the disease (like classic vaccines such as for influenza), but to treat it once there is an outbreak.

Prototype

The prototype vaccine, jointly designed by the pharmaceutical companies Merck and Moderna (ring any bells?), has genetically sequenced up to 34 tumour neoantigens specific to each patient.

Studies carried out with 157 patients have shown that, combined with a known chemotherapy agent (pembrolizumab - a PD-1 protein-blocking immunotherapy treatment), it reduced the risk of the disease reappearing after 18 months by 44%.

After three years of follow-up, the possibility of recurrence or death has risen to 49% and the risk of metastasis has dropped to 62%. Its side effects are also "mild": fatigue, pain localised to the injection site and random body chills.

Nine injections

The vaccine is injected directly into the muscle mass. That said, a single shot is not enough - nine injections are required, administered every three weeks. Aside from the time taken for the injections, another six to eight weeks are needed to manufacture the specific vaccine for each patient.

Oncologists believe that the vaccine will be used initially to prevent any reoccurrence of melanoma and then, over time, it could be expanded to treat cases of metastasis.

A new era

Results obtained to date are so encouraging that experts are confident that this approach will also help treat the following diseases: all non-small cell lung cancers (NSCLC), which account for between 80% and 90% of lung cancer cases; hepatocellular carcinoma (HCC) liver cancer - the most common primary cancer linked to cases of chronic hepatitis and cirrhosis; and the very malignant, triple-negative breast cancer (TNBC), which represents 15% of all breast cancer cases.

All good news then, as summed up by the oncologist: "A new era has begun against cancer."

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