Fighting Cancer with BioTech – Why mRNA Vaccines Are Such a Leap Forward

The mRNA Revolution

When the COVID-19 pandemic struck, the world’s medical community initially prepared for a disaster of the scale of the Spanish Flu, which struck during WW1 and killed 50 million people (from a much smaller global population). Instead, “only” 7 million people are considered to have died from Covid.

mRNA vaccines were, at the time, a novel technology and have been deployed extremely rapidly during/since the pandemic. What made the mRNA vaccine unique compared to previous vaccine technology is the simplicity of development. Previous vaccines would have required finding the exact protocol to inactivate or weaken the virus particles, figure what makes it virulent and how the immune system detects it, and months or years of testing to check if it actually worked.

mRNA vaccines instead can directly look at the virus genome, data that was acquired in the first week after the discovery of Covid-19. And then create an mRNA sequence corresponding to one of the virus, making the patient’s body produce that protein.

This way, the immune system learns to react to the virus protein directly and is ready to be activated when exposed to the real virus.

Source: ESCO Life Sciences

Because the process from virus discovery to vaccine creation is just a few weeks and is mostly driven by genomic data, this has been compared to “writing code” for medicine instead of the more painstakingly slow classical bioresearch.

This creates hope that other diseases that have been resistant to vaccination so far could be prevented with mRNA vaccines. For example:

• Moderna (MRNA ) is working on mRNA vaccines for RSV, EBV (mononucleosis), HSV (herpex), VZV (varicella), HIV, norovirus, Lyme disease, Zica, Nipah, and mPox vaccines
• BioNTech (BNTX ) is working on mRNA vaccines for HSV, tuberculosis, malaria, mPOX, and shingles
• Curevac (CVAC ) also works on mRNA vaccines for bird flu, Lassa yellow fever, RSV, rabies, malaria, and rotavirus.

Going Beyond Infectious Diseases

As the mRNA vaccine works by training the immune system to focus on a given target, determined by its genetic sequence, it can theoretically be trained to attack any type of specific protein, not just infectious diseases.

We also know that cancer cells display specific markers absent in healthy cells. This is the basis of all cancer immunotherapies, like for example CAR-T therapies and monoclonal antibodies, which we discussed in “Monoclonal Antibodies: The Original Precision Therapy”.

The issue is often properly to train the immune system to detect these cancer cells, as custom manufacturing of antibodies of immune cells in labs is expensive and hard to scale up.

This is exactly what mRNA-based cancer therapy is looking to achieve. And progress is being made quickly.

mRNA Lung Cancer Clinical Trials

At the end of August 2024, mRNA vaccine leader BioNTech (producer of the “Pfizer vaccine”) announced that it started global clinical trials in 7 countries and 34 research sites for a mRNA-based lung cancer vaccine, called BNT116.

The focus will be non-small cell lung cancer (NSCLC). It will involve around 130 patients, who will receive BNT116 in combination with immunotherapy, with the goal to boost the efficiency of the treatment.

The trial will enroll patients at different stages of NSCLC, from early-stage disease before surgery or radiotherapy (Stage 2 and 3) to late-stage disease (Stage 4) or recurrent cancer.

It is a more complex therapy than mRNA vaccines like the Covid-19 vaccines, as it includes six consecutive injections five minutes apart over 30 minutes, with each jab containing different RNA strands. The patient will then go on to get the vaccine every week for six consecutive weeks, and then every three weeks for 54 weeks.

Reducing Re-Occurrence

A key expected effect of the mRNA treatment is to reduce the re-occurrence of cancer once the treatment is done, as the effects are expected to be much more lasting than with classical immunotherapies.

This is because the “trained” immune cells will stay active and vigilant against the cancer market, the same way they would be against the risk of a future infectious disease attacking the body.

This also means that while the treatment is not preventing cancer, if it works, it will truly deserve the “vaccine” qualification, at least against cancer re-occurrence.

Other mRNA Applications

Because of its versatility in leveraging the immune system, mRNA technology could be used for a variety of ailments beyond infectious diseases and cancers.

Among the various possible applications, we can mention:

• Rare diseases and genetic diseases: including cystic fibrosis and phenylketonuria.
• Diagnostics: as cancer cells express different protein profiles than normal ones, their mRNA coding for these proteins also differs. This can open the way for cancer detection through a technique called liquid biopsy.
  • Such diagnostic tools will allow for early cancer detection, dramatically increasing the survival rate.
• Heart attacks and healing damaged organs: Researchers at Penn Medicine are using mRNA to modify liver genes and reduce heart attack risks. They are also working on a cure for fibrosis in the heart tissues, a major cause of heart failure.
• Safer gene therapies: While most gene therapies look to insert DNA into cells or to modify DNA using CRISPR technology, this can have unintended consequences as the insertion is permanent.
  • For more transient effects that still rely on gene therapy, injection of mRNA into cells can be used, although this technique is still very recent, and appropriate mRNA delivery systems have only been developed in the last few years.
• Auto-immune diseases: mRNA vaccine can be used to reduce instead of stimulate the immune system response, which is required in auto-immune diseases, where the body attacks healthy cells.
  • This can be achieved by inducing the proliferation of Regulatory T cells (Treg), which reduce the intensity of the erroneous immune reaction.

mRNA Risks

After the quick emergency unrolling of the mRNA vaccine during the pandemic, many feared that it was actually causing plenty of unintended side effects, like heart inflammation (myocarditis).

Combined with the politicization of the vaccines and the chaos of lockdowns and the pandemic, this has led to a lot of confusion.

A few years later, we are now starting to get strong data. While rare, the cases of myocarditis are real, and according to the CDC, “have most frequently been seen in adolescent and young adult males within 7 days after receiving the second dose of an mRNA COVID-19 vaccine”.