Germany-based BioNTech, the company that developed the COVID-19 mRNA vaccine with Pfizer, has announced an mRNA cancer vaccine for colorectal cancer. I hate to get excited about new technologies, but mRNA vaccines could lead to a lot of advances in medicine.
Let’s take a look at this new therapy for colorectal cancer, one of the deadliest cancers.
What is an mRNA cancer vaccine?
As most of you know, the Pfizer 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 the process called transcription, RNA polymerase makes a copy of a gene from its DNA to mRNA as signaled by the cell. 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, where tRNA triplets, which code for one amino acid, attach to the appropriate mRNA triplet, adding one amino acid to the protein chain.
As in DNA, 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, though I took years of courses in cell biology, so trust me when I say I barely touched the surface. If you want to take a deep dive into the science of mRNA and mRNA vaccines, Edward Nirenberg wrote two articles that will satisfy your desires – they make it clear how this all works and doesn’t work.
However, here’s a basic video that shows how this works.
When an mRNA strand exits the nucleus and enters the cytoplasm, it attaches to ribosomes, and this is where protein synthesis progresses. The ribosome reads the base sequence of the mRNA, three bases at a time. Each three-base triplet, called a codon, specifies a particular amino acid, except for a few with regulatory functions (e.g., UGA =“Stop!”).
If the first three-base codon is AUG, then a molecule of the amino acid methionine is brought into place. If the next triplet is AAA, that brings in the amino acid lysine. The methionine and lysine molecules are attached together. The next triplet is, say, GCC, and that brings in alanine, which is attached to the lysine. The ribosome has read nine bases, AUGAAAGCC, and compiled a short chain of three amino acids, abbreviated Met-Lys-Ala, or MKA (see amino acid abbreviations here).
The ribosome continues reading all of the mRNA bases until it hits a stop signal—which is also a triplet codon such as UGA—and the now long chain of amino acids falls loose. This chain may be a functional protein immediately, or, more usually, it might undergo some additional post-translational processing by enzymes to become active.
Once the mRNA has created a number of the proteins, such as the ones that are the goal of mRNA vaccines, that mRNA molecule is then ripped apart by enzymes in the cell so that the individual RNA nucleotides can go back to being reused in a whole new mRNA sequence. The cellular machinery of translating DNA into proteins is constantly recycling RNA.
The mRNA vaccine technology relies upon a specific mRNA sequence to kickstart the endogenous production of proteins that are structurally equivalent to the antigens that will be targets of the vaccine. The mRNA sequences in the vaccine enter the cell (with a carrier protein), and head to the ribosomes to create the viral or cancer antigens. These antigenic proteins will depart the cell and will trigger the body’s adaptive immune system to produce antibodies effective against the intended target, whether it will be cancer cells or viruses.
One more thing – the proteins produced by these mRNA sequences in the vaccines are biologically inert. They will induce an immune response, but they will not cause any other biological effect including becoming pathogenic or causing cancer.
So, let’s summarize. The mRNA vaccines make use of the cell’s ribosome to create the viral or cancer antigens. That antigen induces an adaptive immune system response that will “remember” that antigen allowing the immune system to quickly attack the virus if it shows up.
Someone used this analogy to describe how mRNA works. Let’s say you have a book that represents the genetic code (lots of people describe our genetic code as the official manual of each person). You then scan that book into a copy machine, and now you have a bunch of papers that are an image of the original book. The copy does not change the original book.
I need to make a final point. Cancer “vaccine” is a bit of a misnomer. These vaccines do induce an immune response, but they are not preventative like vaccines for pathogens – they are used as treatments. They are sometimes called “therapeutic vaccines.”
This mRNA cancer vaccine is individualized, meaning it codes for antigenic proteins on each person’s colorectal cancer cells – every 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. But it does not cause one to be resistant to colorectal (or any other cancer). Moreover, these cancer vaccines are usually used in conjunction with surgery and chemotherapy, not as a replacement.
This mRNA cancer vaccine ought to be considered immunotherapy rather than a preventative vaccine, but the name has stuck, so I’ll continue to use it.
BioNTech, which became famous during the COVID-19 pandemic, announced that the first colorectal cancer patient has been treated with its individualized mRNA cancer vaccine BNT122 in a Phase 2 clinical trial. The study plans to enroll about 200 patients with stage II/III colorectal cancer to evaluate the effectiveness of BNT122 compared to “watchful waiting” after surgery and chemotherapy, considered to be the current standard of care for high-risk patients.
The study will be conducted in the USA, Germany, Spain, and Belgium.
The vaccine, called “autogene cevumeran,” is individualized neoantigen-specific immunotherapy (iNeST) – in other words, the immunotherapy has to be individualized to each patient with a specific antigen from the patient’s cancer.
This BioNTech mRNA cancer vaccine employs a different kind of mRNA and a different type of lipid than was used in the COVID-19 vaccine.
The “magic” of these mRNA vaccines is that mRNA sequences can be quickly created and made into a vaccine for each patient presenting with colorectal cancer. Without the mRNA vaccine technology, it could take years to develop this type of immunotherapy, and the patient will probably not be alive at that time.
Of course, this clinical trial is just focused on one cancer. But it is conceivable that other cancers that have antigenic markers that can be recognized by the immune system could be used to develop other cancer vaccines.
No, I do not think this is the end of cancer. This is not a miracle drug. But if the effectiveness holds up in clinical trials, which will probably take many years, it could be a major tool for oncologists to treat colorectal cancer.