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Home » New mRNA vaccine for pancreatic cancer enters phase 2 trials

New mRNA vaccine for pancreatic cancer enters phase 2 trials


I have written a lot about vaccines that treat cancer. Now we have another new mRNA vaccine to treat pancreatic cancer that has shown promising results in phase 1 clinical trials and is now entering a larger phase 2 clinical trial. This is exciting news for a deadly cancer that attacks tens of thousands of people each year.

The mRNA vaccine technology is going to be one of the leading technologies for cancer treatments going forward. If it can make a meaningful dent in the course of pancreatic cancer, it may well become one of the primary tools for oncologists in treating this pernicious disease.

As I usually do, let’s review this vaccine and the clinical trial results.

mRNA vaccines

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.

mRNA cancer vaccine

These mRNA cancer vaccines help create antibodies against specific antigens on the surface of the pancreatic cancer, destroying the cancer in the process. The mRNA vaccine for pancreatic cancer is individualized, that is, each person receives an mRNA vaccine that has been engineered for that person. The mRNA vaccine for cancer developed for person X will probably not work on person Y.

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 pancreatic cancer cells – every person has slightly different antigens even if they have the same cancer type. However, and scientists aren’t sure of this yet, the vaccine actually might reduce the risk of recurrence of the cancer.

The mRNA cancer vaccine trains the immune system to attack the cancer cells that may have been missed by surgery or chemotherapy, or have metastasized to another location. However, it does not cause one to be resistant to colorectal (or any other cancer).

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.

The mRNA vaccine for pancreatic cancer is usually given after recovery from surgery. During the post-surgery period, the mRNA vaccine is created for that individual and given to them as part of the treatment strategy. During and after receiving the vaccine, the patient will probably also receive chemotherapy. According to clinical research, this is the best way to have the highest success rate.

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.

Pancreatic cancer mRNA vaccine

Before I discuss the vaccine, here are some facts about pancreatic cancer:

  1. An estimated 66,440 people (34,530 men and 31,910 women) will be diagnosed with pancreatic cancer in 2024.
  2. About 51,750 people (27,270 men and 24,480 women) will die of pancreatic cancer in 2024.
  3. Because early symptoms of pancreatic cancer may be missed, it is usually diagnosed in later stages which leads to only a one-year lifespan after diagnosis.
  4. Treatment of pancreatic cancer usually requires surgery plus adjuvant therapies like chemotherapy and radiation therapy. Of course, the success rate of this strategy is lower with later-stage pancreatic cancer.

Thus, additional tools like an mRNA vaccine to treat the cancer help increase the success rate of pancreatic cancer treatments.

The pancreatic cancer mRNA vaccine, cevumeran, was developed by BioNTech, the German pharmaceutical company that developed one of the COVID-19 mRNA vaccines in partnership with Pfizer. Phase 1 clinical trial results were published last year, which showed 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.

The phase 2 clinical trial, sponsored by Genentech and BioNTech, is recruiting 260 patients to participate in 14 locations in the USA. The study will compare the endpoints of patients with pancreatic cancer who receive cevumeran plus Atezolizumab and mFOLFIRINOX, two chemotherapy drugs, to patients who receive mFOLFIRINOX alone. The goal of the study is to determine the safety and efficacy of cevumeran, the mRNA vaccine, and to determine if the vaccine improves outcomes compared to chemotherapy alone.

Patients undergo surgery to remove the tumor, which is then sequenced to make a personalized vaccine specific to the patient’s cancer. The vaccine is developed in four to six weeks while patients recover from surgery. Patients receive six weekly injections, and following six months of standard chemotherapy, patients receive six more vaccines as boosters.

Summary

I have seen many great advances in disease treatment during my life, everything from human insulin for the treatment of type 1 diabetes to a long list of cancer treatments that have led to improved lifespans after a cancer diagnosis. But this mRNA vaccine technology is a game changer.

We still do not have enough data to say whether these vaccines work for all cancers, but preliminary data supports their use in improving the lifespan of people who have developed these deadly cancers.

If this pancreatic cancer vaccine works, and we will know in a few years, it can dramatically improve the odds of surviving a pancreatic cancer diagnosis.

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.
Michael Simpson

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