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Home » New mRNA vaccine for melanoma shows promising results

New mRNA vaccine for melanoma shows promising results


Moderna and Merck have presented promising results from their phase 2b clinical trial that investigated a combination of a mRNA vaccine and the cancer drug Keytruda (pembrolizumab) for the treatment of melanoma. This is the start of a lot of studies that are examining new mRNA vaccines for the treatment, and occasionally prevention of, various cancers.

I have reviewed results from earlier clinical trials for this new vaccine. However, this article will take a look at the newest results from the clinical trial for this vaccine to treat melanoma.

doctor writing on a medical chart
Photo by RDNE Stock project on Pexels.com

What is the mRNA cancer vaccine for melanoma?

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 transcription process, RNA polymerase makes a copy of 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 that eventually 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 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.

The mRNA vaccines essentially inject mRNA fragments that code for key antigens which 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 do induce an immune response, but they are not preventative like vaccines for pathogens – they are used as treatments. 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. However, it does not cause one to be resistant to any 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 cells 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 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 should be considered immunotherapy rather than a preventative vaccine, but the name has stuck, so I’ll continue using it.

Let me review all of this science quickly:

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

Clinical trial results for melanoma vaccine

In a phase IIb study, investigators examined the effectiveness of combining the Moderna mRNA vaccine (mRNA-4157 [V940]) with Merck’s cancer drug Keytruda as a potential adjuvant therapy (to surgery) for high-risk melanoma.

Here are some of their key results:

  • Treatment with mRNA-4157 (V940) in combination with Keytruda led to a clinically meaningful improvement in recurrence-free survival, reducing the risk for recurrence or death by 49%, compared with Keytruda alone. Simply, the mRNA vaccine plus KEYTRUDA cut the risk of death or recurrence of melanoma by nearly half.
  • The combination of mRNA-4157 (V940) with Keytruda also continued to demonstrate a meaningful improvement in distant metastasis-free survival compared with pembrolizumab alone, reducing the risk of developing distant metastasis or death by 62%. Simply, the combination showed a large improvement in lowering the risk of death over the long term.

These are amazing numbers in the treatment of high-risk melanomas. Sometimes, cancer treatments are approved when they only show a few percentage point decrease in metastasis or death.

I am not saying that mRNA vaccines are a miracle treatment for cancer, but they are showing some incredible promise as an adjuvant therapy that will give oncologists better tools to kill cancer and possibly stop its reoccurrence.

Considering few of us knew about mRNA vaccines just three years ago (I study vaccines, and I didn’t know much about them).

Moderna and Merck are recruiting participants in pivotal phase III clinical trials, and possibly get fast-track approval in two to three years. I don’t know when the clinical trial will start recruiting, but I will update this post with that information once I have it.

This is an exciting use of the mRNA vaccines that has great promise for the future. The mRNA vaccines stopped the COVID-19 pandemic in its tracks, and individualized versions of the vaccine may help treat some dangerous cancers. I’m glad that the inventors of the vaccine won the Nobel Prize, they’ve done more for humanity than most people.

Citations

Michael Simpson
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