Since the advent of vaccines to stop the COVID-19 pandemic, the mRNA vaccines have become well known. Despite the anti-vaccine claims, these mRNA vaccines are safe and effective. But what you may not know is that an mRNA vaccine can be used to treat cancer, like pancreatic cancer.
I have written previously about this mRNA vaccine, called cevumeran, to treat colorectal cancer, now the same vaccine can also be used to treat pancreatic cancer, which is one of the tougher cancers to treat effectively.
I think that various versions of an mRNA vaccine can be developed to treat several different cancers, for this article, we are going to look at early published results from a clinical trial for the treatment of pancreatic cancer.
What is the mRNA pancreatic 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 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 code 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. But it does not cause one to be resistant to colorectal (or any other 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.
mRNA vaccine for pancreatic cancer research
In a paper published on 10 May 2023 in the respected scientific journal, Nature, Vinod Balachandran, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues provided early results from a clinical trial on the effect of the mRNA vaccine cevumeran on pancreatic cancer compared to standard treatment.
Currently, surgery is the only curative treatment for the disease. Unfortunately, almost 90% of patients have disease recurrence at a median of 7 to 9 months. Adjuvant multi-agent chemotherapies can delay recurrence in surgically resected pancreatic cancer, but nearly 80% of patients have disease recurrence by 14 months.
In this trial, cevumeran, an individualized neoantigen vaccine, the investigators synthesized mRNA neoantigen vaccines in real-time from surgically resected pancreatic tumors. After surgery, the researchers sequentially administered a single dose of immunotherapy, followed by cevumeran and a modified chemotherapy regime.
The researchers found some promising results. At a median follow-up of 18 months after surgery, eight patients who had immune responses to the mRNA vaccine, cevumeran, had significantly longer recurrence-free survival compared with a median of 13.4 months in the eight patients who had no immune response. This is great news.
Also, one patient showed evidence of a vaccine-induced response in the liver after developing an unusual 7-mm lesion there.
Of the patients who received cevumeran, none developed a serious adverse event. Now, it’s hard to tell adverse events as the patients are also on chemotherapy at the same time.
Finally, even though this was a small clinical trial, it showed outstanding promise for the mRNA vaccine to treat pancreatic cancer. More than that, it seems to show promise that the cancer won’t return.
Summary
Although mRNA vaccines have become a breakthrough in preventing infectious diseases, their use in treating cancer is where we can find true excitement. Oncologists can create personal “vaccines” that can help the immune system attack these cancers that can “avoid” being attacked without the vaccine.
I’m not saying that the mRNA vaccines will “cure” cancer. However, even though we are early in the research, there is a lot of early evidence that it can become a powerful tool for oncologists to conquer very difficult-to-treat cancers.
And because the immune system is “trained” by these vaccines to recognize the individual’s pancreatic cancer, it can also help prevent future recurrence.
I was excited about mRNA vaccines for stopping various infectious diseases. Now I am doubly excited about its potential in treating cancer.
Citations
- Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, Lihm J, Ceglia N, Guasp P, Chu A, Yu R, Chandra AK, Waters T, Ruan J, Amisaki M, Zebboudj A, Odgerel Z, Payne G, Derhovanessian E, Müller F, Rhee I, Yadav M, Dobrin A, Sadelain M, Łuksza M, Cohen N, Tang L, Basturk O, Gönen M, Katz S, Do RK, Epstein AS, Momtaz P, Park W, Sugarman R, Varghese AM, Won E, Desai A, Wei AC, D’Angelica MI, Kingham TP, Mellman I, Merghoub T, Wolchok JD, Sahin U, Türeci Ö, Greenbaum BD, Jarnagin WR, Drebin J, O’Reilly EM, Balachandran VP. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023 May 10:1–7. doi: 10.1038/s41586-023-06063-y. Epub ahead of print. PMID: 37165196; PMCID: PMC10171177.
