BioNTech has announced their promising new lung cancer mRNA vaccine candidate, BNT116, will begin phase 2 clinical trials. The company says BNT116 works by “presenting the right set of antigens for each cancer indication to the immune system,” to “activate immune cells that recognize cancer-specific antigens and turn them against the cancer cells.”

I think most people would be excited about a new tool to fight lung cancer, but I’m sure anti-vaccine activists will dismiss it because of unscientific reasons, especially since it uses the mRNA vaccine technology. However, mRNA technology may provide vaccines to treat melanoma, colorectal, and other cancers.

This article will examine how the lung cancer mRNA cancer vaccine works and what is happening in the clinical trials.

How do mRNA cancer vaccines work?

As most of you know, the Pfizer/BioNTech and Moderna Therapeutics COVID-19 vaccines are mRNA vaccines that rely upon an mRNA, or messenger RNA, molecule to induce an immune response. However, it does not do this directly.

Normally, during transcription, an RNA polymerase enzyme copies a gene from the cell’s DNA and converts it to mRNA. In other words, the mRNA sequences in the cell usually correspond directly to the DNA sequences in our genes. These mRNA sequences “carry” that genetic message to a ribosome for translation into amino acid sequences which become one of the thousands of proteins necessary to live.

As in DNA, the genetic information in mRNA is contained in the sequence of nucleotides arranged into codons consisting of three ribonucleotides each. Each codon codes for a specific amino acid, except the stop codons, which terminate protein synthesis.

At this point, note that the mRNA does nothing to the DNA strand in your genes – the mRNA merely provides the information to the cell to produce a protein.

Yes, that’s a lot of cell biology, so trust me when I say I barely touched the surface. If you want to examine the science of mRNA and mRNA vaccines, Edward Nirenberg wrote two articles that will satisfy your desires – they show how this all works and doesn’t work.

These mRNA vaccines inject the mRNA fragments that code for key antigens that are absorbed into cells. The fragments then go to the ribosomes to produce the antigens inducing the adaptive immune system to “remember” those antigens, attacking them when they are present like when an infectious pathogen enters the body. In the case of cancer “vaccines,” the mRNA codes for key unique antigens on the targeted cancer that is found in the cancer patient.

I need to make a final point. Cancer “vaccine” is a bit of a misnomer. These vaccines induce an immune response — however, they are not preventative like vaccines for pathogens. These cancer vaccines are treatments. Moreover, the mRNA cancer vaccine is individualized, meaning it codes for antigenic proteins on each person’s colorectal cancer cells – each person has slightly different antigens even if they have the same cancer type.

The mRNA cancer vaccine trains the immune system to attack the cancer cells that may have been missed by surgery or chemotherapy. However, it does not cause one to be resistant to the cancer. The mRNA cancer vaccine must be created for each individual — the key antigens on the surface of the cancer, which are unique to every person, are used to create the mRNA vaccine.

Then like the COVID-19 vaccine, the vaccine is injected and it causes the cell to produce those antigens that train the immune system to attack the cancer. Moreover, a cancer vaccine for one person probably cannot be used for another person, because the antigens are so unique.

Furthermore, these cancer vaccines are usually used in conjunction with surgery, and possibly chemotherapy, as part of an overall treatment strategy for cancer. These mRNA cancer vaccines ought to be considered immunotherapy rather than a preventative vaccine, but the name has stuck, so I’ll continue to use it.

Let me review all of this science quickly:

1. Although this is not a preventative vaccine, it can cause the immune system to attack any recurrence of that cancer in the future.
2. The mRNA vaccine is tailored for the individual because cancer antigens vary slightly from person to person even for the same cancer.
3. The cancer antigen mRNA is harvested from the individual and is used to create the mRNA fragment to be used in the vaccine.
4. The vaccine is used mostly as a treatment — it induces the immune system to attack the cancer.

The BioNTech mRNA lung cancer vaccine

Germany’s BioNTech has a cancer vaccine candidate called BNT116 (there will be a fancy name when a new drug application is sent to the FDA). It is an mRNA vaccine designed to treat advanced non-small cell lung cancer, the most common form of lung cancer.

The vaccine is currently being evaluated alone and in combination with a monoclonal antibody medication in a phase 2 trial. The trial will be conducted in seven countries and will establish safety profile and dosing. The phase 3 trials, which will begin after the completion and evaluation of the phase 2 trials, will give researchers better information about the vaccine effectiveness.

BioNTech says that BNT116 is currently being evaluated in phase 2 trials to establish a safety profile and safe dose. Generally, phase 2 trials do not include effectiveness goals, but frequently, researchers can get a good idea of whether the vaccine works or not. The vaccine is being evaluated alone and in combination with the monoclonal antibody medication for cancer, cemiplimab.

Technically, BNT116 is an mRNA cancer vaccine designed to encode six shared lung cancer–associated antigens frequently expressed in non-small cell lung cancer. The vaccine is based on BioNTech’s “FixVac” platform, which consists of “a fixed combination of mRNA-encoded non-mutated tumor antigens, which are known to frequently express within specific cancer types.”

In other words, BioNTech says BNT116 works by “presenting the right set of antigens for each cancer indication to the immune system,” to “activate immune cells that recognize cancer-specific antigens and turn them against the cancer cells.”

Summary

I hate to get excited about a vaccine that is years away from becoming widely available, but this mRNA vaccine technology to treat non-small cell lung cancer, which kills over 80% of people who are diagnosed with it, is very exciting.

This phase 2 clinical trial will probably not be completed until 2027, and at that time, we will get some more information about the safety and, possibly, the effectiveness of the lung cancer mRNA vaccine.

The mRNA vaccines are some of the most promising technologies to add to the armamentarium of oncologists to effectively treat many cancers.