Madhura Kadam—McMaster Biology & BND 2023
We are very close to a pancreatic cancer vaccine. Indeed, there are currently many clinical trials being conducted that are testing the efficacy of various pancreatic cancer vaccines candidates—some with promising preliminary results.
To provide some background, pancreatic cancer is the fourth most common cause of cancer death in the U.S.3. Pancreatic cancers occur when cells in the pancreas are damaged, causing them to grow out of control3. Current treatments available to treat pancreatic cancer include surgery, chemotherapy, radiation therapy, immunotherapy and dietary changes2. Vaccines that treat cancers, also known as therapeutic vaccines, are a type of cancer treatment called immunotherapy1. These vaccines work to boost the immunity of the patient to fight cancers1.
Figure 1. Image depicting pancreatic cancer. Adapted from the National Cancer Institute9
There are currently many promising clinical trials underway testing vaccines for pancreatic cancer. One of the most successful trials was conducted by Dr. Balachandran in collaboration with the BioNTech company5. They created a mRNA vaccine that targeted neoantigen proteins5. Neoantigens are proteins present on the cancer that alert the immune system of the presence of abnormal development in the body to stop the cancer from spreading5. In 8 of the 16 patients, the vaccine activated T cells of the immune system that recognize the patient’s own pancreatic cancer cells, triggering the immune system to attack the cancer6. There were also delays in the recurrence of pancreatic cancers in these patients5. These findings suggest that T-cell activation of the immune system through the vaccine may have the desired effect of keeping pancreatic cancer in check.
Figure 2. Targeting neoantigen proteins. Adapted from Pearlman et al8
Figure 3. Mechanism for the functioning of cancer vaccines. Adapted from Roy7
mRNA vaccines are created by genetically sequencing the neoantigens proteins in the pancreatic tumors of patients5. The genetic sequences of neoantigens act as a template for making mRNA vaccines. When the vaccine is injected into the person’s bloodstream, it causes the immune cells known as dendritic cells to make the neoantigen proteins5. The dendritic cells train the rest of the immune system to recognize and attack tumor cells expressing the same neoantigen proteins5. Since the immune system is aware of neoantigens as a “harmful protein” to the body, the cancer may have less chance of returning as it is most likely to be destroyed by the immune system5.
Another vaccine developed by Elizabeth Jaffee, M.D., and Daniel Laheru, M.D., is also currently in the clinical trial phase1. This vaccine uses pancreatic cancer cells that are treated with radiation to inhibit their ability to grow1. These cancer cells are also altered genetically to secrete a molecule called GM-CSF1. This molecule attracts immune system cells to the site of the tumor vaccine where they encounter antigen proteins of the radiated cells1. Once these antigens are recognized, this trains the immune system to attack any remaining pancreatic cancer cells in the body1. The mechanism for this vaccine is like that of the mRNA vaccine mentioned above, but the specific proteins and antigen targets that are used differ between the two treatments.
Many other clinical trials for pancreatic cancer vaccines are also currently under development4. These trials include vaccines that are cell based, DNA-based, peptide based and microorganism based4. In summary, many pancreatic cancer vaccines are currently under development at different stages of testing. More clinical testing and FDA approval is required for these vaccines to be commercially available, however the advancements in current vaccinations point to a hopeful future for vaccines to be an effective treatment for pancreatic cancers.
- Hopkins Medicine. Pancreatic cancer vaccine [Internet]. Pancreatic Cancer Vaccine | Johns Hopkins Medicine. 2022 [cited 2022Nov27]. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer/pancreatic-cancer-vaccine
- Hopkins Medicine. Pancreatic cancer treatment [Internet]. Pancreatic Cancer Treatment | Johns Hopkins Medicine. 2022 [cited 2022Nov28]. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer/pancreatic-cancer-treatment
- Hopkins Medicine. Pancreatic cancer [Internet]. Pancreatic Cancer | Johns Hopkins Medicine. 2022 [cited 2022Nov28]. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/pancreatic-cancer
- Huang X, Zhang G, Tang T-Y, Gao X, Liang T-B. Personalized pancreatic cancer therapy: From the perspective of mrna vaccine – military medical research [Internet]. BioMed Central. BioMed Central; 2022 [cited 2022Nov28]. Available from: https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-022-00416-w/tables/2
- MSKCC. MSK mrna pancreatic cancer vaccine trial shows promising results [Internet]. Memorial Sloan Kettering Cancer Center. 2022 [cited 2022Nov28]. Available from: https://www.mskcc.org/news/can-mrna-vaccines-fight-pancreatic-cancer-msk-clinical-researchers-are-trying-find-out
- Page ML. Pancreatic cancer vaccine: What to know about early promising results [Internet]. New Scientist. New Scientist; 2022 [cited 2022Nov28]. Available from: https://www.newscientist.com/article/2323437-pancreatic-cancer-vaccine-what-to-know-about-early-promising-results/
- Roy S. Cancer vaccines: Are we there yet? [Internet]. Cancer Vaccines: Are We There Yet? | Vanderbilt Institute for Infection, Immunology and Inflammation. 2020 [cited 2023Jan4]. Available from: https://www.vumc.org/viiii/immuknow/cancer-vaccines-are-we-there-yet
- Pearlman AH, Hwang MS, Konig MF, Hsiue EH-C, Douglass J, DiNapoli SR, et al. Targeting public neoantigens for cancer immunotherapy [Internet]. Nature News. Nature Publishing Group; 2021 [cited 2023Jan4]. Available from: https://www.nature.com/articles/s43018-021-00210-y
- National Cancer Institute. Pancreatic cancer treatment (adult) (PDQ®)–patient version [Internet]. National Cancer Institute. 2020 [cited 2023Jan4]. Available from: https://www.cancer.gov/types/pancreatic/patient/pancreatic-treatment-pdq