Cancer Preventing Vaccines: Unleashing the Potential of Tumor Antigens

Posted on by Sara Christenson

It has been more than 100 years since Dr. William B. Coley, known today as the “Father of Immunotherapy,” made the first recorded attempt to mobilize the immune system as a means of treating cancer (9). Decades later, the discovery of T cells and the vital role they play in the immune system set the groundwork for many new immunotherapy treatments, such as those involving monoclonal antibodies, cytokines, CAR T cells, and checkpoint inhibitors.

Although researchers were aware of the immune system’s ability to detect and attack tumors by recognizing specific antigens, it wasn’t until 1989 that the first human tumor-associated antigen was discovered by Olivera Finn (5). From there, researchers began rapidly identifying hundreds of different tumor antigens, many of which were quickly developed into a new type of immunotherapy–vaccines to treat cancer.

But despite more than two decades of research and promising results in animal trials, most vaccines to treat cancer weren’t successful when tested in a clinical setting (4). However, this was likely due to their exclusive use as a therapeutic treatment, rather than a preventative one. Most cancer patients have a suppressed immune system due to their cancer or the cancer treatments they have received, which makes it difficult for a therapeutic vaccine to elicit a potent immune response (4). As a result, many researchers have turned their focus from vaccines that can treat cancer towards those that can prevent it.

How do Cancer Preventing Vaccines Work?

The objective of a preventative cancer vaccine is to trigger a strong primary adaptive immune response, enabling a prompt and robust secondary response in the event carcinogenesis occurs (6). To accomplish this, prophylactic cancer vaccines introduce either tumor-specific antigens (TSAs), which are present only on tumor cells, or tumor-associated-antigens (TAAs), which are found in small quantities on some healthy cells but are overexpressed on tumor cells (10). Upon recognition of the tumor antigens, the immune system activates the adaptive immune response, stimulating the production of T cells and B cells (3). The immune system also develops immunological memory of the antigen, allowing it to mount a quick and strong immune response if the antigen is recognized on a tumor in the future.

Cancer-preventing vaccines can utilize a single TAA or TSA, or they can employ a large variety of antigens in an attempt to protect against a wide range of cancers. However, researchers are concerned that a vaccine utilizing TAAs, which are already present in healthy cells in small amounts, could result in an autoimmune reaction (14). Because of this, many researchers are focusing their efforts on vaccines that solely utilize TSAs. Although TSAs greatly reduce the concern of an autoimmune attack, they aren’t without their own challenges. Most TSAs are unique to the cancer of an individual patient, which presents a challenge for researchers who must predict antigens in advance (12). Some TSAs, however, do consistently appear on the tumors of many different individuals, making them prime candidates for preventative cancer vaccines.

Current Research on Cancer Preventing Vaccines

Although there are currently no approved cancer preventing vaccines, there are several clinical trials taking place across the United States.

One of these trials, taking place at Penn Medicine’s Abramson Cancer Center, is testing a DNA vaccine targeting the hTERT antigen, which is found on many breast, ovarian, and prostate cancers (11). The study began in April of 2021 and is currently testing the safety and immune responses to the vaccine in 44 participants with BRCA1 or BRCA2 mutations who have either never had cancer or are in remission.

The BRCA1 and BRCA2 genes, which are known as tumor suppressor genes, are responsible for repairing damaged DNA that can lead to cancer and uncontrolled tumor growth (7). Certain mutations, however, can prevent the BRCA genes from functioning properly. Because of this, the BRCA mutations, which are found in about 1 in 400 people, are responsible for a significantly heightened lifetime risk of breast, ovarian, and prostate cancer (8).

A primary trial for this vaccine was conducted to test its safety in 93 patients in remission. During this trial, all but four patients produced T cells that home in on hTERT, and of the 34 patients in remission from pancreatic cancer, 41% were still cancer free after 18 months (typically pancreatic cancer returns within 12 months). The study is expected to be completed in 2025.

Another trial, focusing on a pancreatic cancer-preventing vaccine, began at Johns Hopkins’ Sidney Kimmel Comprehensive Cancer Center in May of 2022 (13). The Hopkins’ team is testing a vaccine containing mutated KRAS peptides in 25 patients with an elevated risk for pancreatic cancer due to an inherited mutation or a family history. In the case of pancreatic cancer, the KRAS gene is one of the first ones to get mutated. Because of this, the Hopkins’ team believes that the vaccine will be able to prevent pancreatic tumor cells from proliferating. Overall, the study will be evaluating the vaccine’s ability to produce mutant-KRAS-specific T cells, as well as the vaccine’s safety.

Another noteworthy trial, currently being sponsored by the National Cancer Institute, is testing an ambitious vaccine containing viruses engineered to transport DNA for 209 different TSAs present in Lynch Syndrome tumors (1). Lynch Syndrome is an inherited genetic mutation that causes an individual’s mismatch repair genes to not function properly (2). Individuals with Lynch syndrome have up to an 80 percent lifetime risk of colorectal cancer, a 60 percent lifetime risk of endometrial cancer, and an increased risk of many other cancers, such as gastric, ovarian, small bowel, urothelial, biliary tract, pancreatic, brain, and others. 

Because TSAs differ across individuals, and immune systems vary in how they react to different TSAs, a vaccine that could target such a wide range of TSAs would be revolutionary. In September 2022, 45 people with Lynch syndrome who were cancer-free or in remission received the vaccine as part of the study (1). As the study progresses, the researchers will evaluate whether the vaccine triggers a strong immune response, as well as if it has any effect on developing tumors.  If the trial produces positive results, researchers will further the investigation by conducting a randomized study of hundreds of patients over the next 5 to 10 years.

Conclusion

While further research is still needed, these vaccines offer a glimmer of hope for those whose genetic mutations increase their risk of cancer.

References

  1. Bansal, A. (2023, March 22 – 2027, February 1). Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome. Identifier NCT05419011. Retrieved from https://clinicaltrials.gov/ct2/show/NCT05419011
  2. Bhattacharya P, McHugh TW. Lynch Syndrome. [Updated 2023 Feb 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431096/
  3. Crews, D. W., Dombroski, J. A., & King, M. R. (2021). Prophylactic Cancer Vaccines Engineered to Elicit Specific Adaptive Immune Response. Frontiers in oncology, 11, 626463. https://doi.org/10.3389/fonc.2021.626463
  4. Finn O. J. (2014). Vaccines for cancer prevention: a practical and feasible approach to the cancer epidemic. Cancer immunology research, 2(8), 708–713. https://doi.org/10.1158/2326-6066.CIR-14-0110
  5. Finn O. J. (2017). Human Tumor Antigens Yesterday, Today, and Tomorrow. Cancer immunology research, 5(5), 347–354. https://doi.org/10.1158/2326-6066.CIR-17-0112
  6. Kangla Tsung & Jeffrey A Norton (2016) In situ vaccine, immunological memory and cancer cure, Human Vaccines & Immunotherapeutics, 12:1, 117-119, DOI: 10.1080/21645515.2015.1073427
  7. Kryzak, A. (2023). BRCA: The Breast Cancer Gene – BRCA Mutations & Risks. National Breast Cancer Foundation. https://www.nationalbreastcancer.org/what-is-brca/
  8. Maxwell, K. N., Domchek, S. M., Nathanson, K. L., & Robson, M. E. (2016). Population Frequency of Germline BRCA1/2 Mutations. Journal of Clinical Oncology, 34(34), 4183–4185. https://doi.org/10.1200/jco.2016.67.0554
  9. McCarthy E. F. (2006). The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. The Iowa orthopaedic journal, 26, 154–158.
  10. Okarvi, S. M., & AlJammaz, I. (2019). Development of the Tumor-Specific Antigen-Derived Synthetic Peptides as Potential Candidates for Targeting Breast and Other Possible Human Carcinomas. Molecules (Basel, Switzerland), 24(17), 3142. https://doi.org/10.3390/molecules24173142
  11. Torres, A. (2021, April 20 – 2025, December). INO 5401 Vaccination in BRCA1/2 Mutation Carriers. Identifier NCT04367675. Retrieved from https://clinicaltrials.gov/ct2/show/NCT04367675
  12. Xie, N., Shen, G., Gao, W. et al. Neoantigens: promising targets for cancer therapy. Sig Transduct Target Ther 8, 9 (2023). https://doi.org/10.1038/s41392-022-01270-x
  13. Zaidi, N. (2022, April 11 – 2026, May 1). Mutant KRAS -Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer. Identifier NCT05013216. Retrieved from https://clinicaltrials.gov/ct2/show/NCT05013216
  14. Zhang, Z., Lu, M., Qin, Y., Gao, W., Tao, L., Su, W., & Zhong, J. (2021). Neoantigen: A New Breakthrough in Tumor Immunotherapy. Frontiers in immunology, 12, 672356. https://doi.org/10.3389/fimmu.2021.672356
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Sara Christenson

Sara Christenson

YouTube Optimization & Social Media Intern at Promega Corporation
Sara is a Marketing Coordinator at Promega. She earned her B.S. in Life Sciences Communication and a certificate in Digital Studies at the University of Wisconsin-Madison.

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