By Bloom Lerngutai, Fall 2023.

The idea of a cancer vaccine may sound like something out of a science fiction novel. While most people have heard of flu or Covid-19 vaccinations, vaccines for cancer are perhaps less widely known. However, they have existed for quite some time—with the first being approved by the FDA in 2010— and are arguably the future of cancer treatment. [1]

Currently, cancer treatment consists of local and systemic treatments. Some examples of local treatments are surgery and radiation, while some examples of systemic treatments are chemotherapy and immunotherapy. While local treatments only affect a certain area of the body or a specific tumor, systemic treatments affect the whole body. [2] While these cancer treatments are effective, personalized treatment such as those of cancer vaccines can have a lesser effect on healthy cells, suggesting a more targeted approach.

Cancer vaccines can be categorized into two types: preventative vaccines and therapeutic vaccines. As the name suggests, preventative vaccines prevent cancer. Common examples include the Human papillomavirus (HPV) vaccine or the Hepatitis B virus (HBV) vaccine. While these vaccines do not directly prevent cancer, they do prevent HPV and HBV which can cause cervical and liver cancer, respectively. Both vaccines have high efficacy, with HPV vaccines having an efficacy of 97% in preventing cervical cancer (through preventing HPV) [3] and HBV vaccines having an efficacy of nearly 100% in preventing hepatitis B [4]. Therapeutic vaccines, on the other hand, are vaccines that act as treatment to cancer by strengthening the body’s immune system and increasing its ability to find antigens on cancer cells in order to kill them. [1] Preventive approaches are advantageous in that they save costs in the long run as they prevent the disease from occurring in the first place, but have the disadvantages of higher immediate cost as well as sometimes low accessibility. Thus, preventive approaches are often used in conjunction with responsive approaches.

A notable subtype of therapeutic cancer vaccines are personalized cancer vaccines. These vaccines would target different abnormal proteins that tumor cells exhibit due to their genetic instability. Cancer is defined as the uncontrolled division of cells, where a cause of cancer are genetic mutations, which are changes to the body’s DNA code. DNA codes for RNA, which codes for proteins—the molecules that function within cells. Thus, a mutation in DNA can lead to abnormal proteins that would otherwise not be found in a regular, healthy cell. To produce a personalized cancer vaccine, antigen sources would be needed to identify possible targets for the vaccine such as resected tumors, RNA, or DNA. Vaccines can be beneficial in preventing cancer recurrence due to immunological memory, where the immune system “remembers” the way to respond to these cancer cells. [2]

A personalized cancer vaccine in the works is mRNA-4157 by Moderna and Merck, who recently launched the phase 3 trial of the melanoma vaccine on July 26, 2023. Phase 3 of clinical trials is the last phase before the drug is approved for general use. In phase 3, the drug is already shown to work but must then be tested to prove whether it works better than the pre-existing treatments. The process of manufacturing the vaccine includes sequencing the patient’s genome from both the tumor and healthy tissue and the resulting identification of tumor-specific mutations. mRNA-4157 is a personalized mRNA that codes for as many as 34 different patient-specific neoantigens. Antigens are agents that induce the body’s immune system to respond. Neoantigens are foreign proteins that do not exist in normal tissue. Therefore, antigens of tumors are considered neoantigens. The mRNA codes for these neoantigens and allows the immune system to strengthen its response to them. [3]

BioNTech has also recently published its findings from a phase 1 trial for a personalized neoantigen mRNA vaccine for pancreatic cancer. The vaccines were synthesized from surgically resected tumors. The results found that neoantigen-specific T cells were generated in substantial amounts in 50% of patients. Although the trial is still in a very early stage, the preliminary results are considered to be promising. [4]

Studies have also demonstrated the increased effectiveness of combinational therapy of cancer vaccines. Kleponis et al. describe the effectiveness of cancer vaccines in combination with immune checkpoint inhibitors. [5] Immune checkpoint inhibitors block the binding of checkpoint proteins with their partners, thus preventing an “off” signal, allowing the T cells to kill cancer cells. [6] T cells are a type of white blood cell. Some types of T cells send signals to other immune cells while others fight the pathogen directly, An issue with immune checkpoint inhibitors is that patients lack sufficient tumor-infiltrating effector T cells. Some cancers cause a lack of T cells, and thus while the “off” signal is prevented, there can still be insufficient “workers”—the T cells—to follow through with the orders. Nonetheless, cancer vaccines work synergistically to induce effector T-cell infiltration. [5]

Currently, there is only one FDA-approved vaccine that directly targets cancer: sipuleucel-T for prostate cancer. While cancer vaccine trials have had a subpar track record with results often showing failure once the vaccine is trialed on larger groups, the mRNA vaccine approach shines a new hope on the landscape as it allows for the targeting of multiple patient-and-tumor-specific neoantigens. [3] 

Following the pandemic, increased attention has been put on biotechnology companies and cancer research, with $21.7 billion being invested by private investors in biotechnology companies in 2022. With the post-pandemic increases in investment, coupled with constantly advancing technology within the field of science, personalized cancer vaccines provide a promising future to cancer treatments.

[1] Wedekind, Sophie. “Cancer Vaccines – Where Are We?” Cancer Research UK – Cancer News, February 24, 2023. https://news.cancerresearchuk.org/2023/02/24/cancer-vaccines-where-are-we/. 

[2] Cancer.Net. “What Are Cancer Vaccines?,” September 30, 2013. https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/what-are-cancer-vaccines.

[3] Carvalho, Thiago. “Personalized Anti-Cancer Vaccine Combining mRNA and Immunotherapy Tested in Melanoma Trial.” Nature Medicine 29, no. 10 (August 16, 2023): 2379–80. https://doi.org/10.1038/d41591-023-00072-0.

[4] “What I Tell Every Patient About the HPV Vaccine.” Accessed November 21, 2023. https://www.acog.org/womens-health/experts-and-stories/the-latest/what-i-tell-every-patient-about-the-hpv-vaccine.

[5] “Hepatitis B.” Accessed November 21, 2023. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b.

[6] Fritah, Hajer, Raphael Rovelli, Cheryl Lai-Lai Chiang, and Lana E. Kandalaft. “The Current Clinical Landscape of Personalized Cancer Vaccines.” Cancer Treatment Reviews Volume 106 (March 24, 2022). https://doi.org/https://doi.org/10.1016/j.ctrv.2022.102383.

[7] Kleponis, Jennifer, Richard Skelton, and Lei Zheng. “Fueling the Engine and Releasing the Break: Combinational Therapy of Cancer Vaccines and Immune Checkpoint Inhibitors.” Cancer Biology & Medicine 12, no. 3 (September 2015): 201–8. https://doi.org/10.7497/j.issn.2095-3941.2015.0046.

[8] Rojas, Luis A., Zachary Sethna, Kevin C. Soares, Cristina Olcese, Nan Pang, Erin Patterson, Jayon Lihm, et al. “Personalized RNA Neoantigen Vaccines Stimulate T Cells in Pancreatic Cancer.” Nature 618, no. 7963 (June 2023): 144–50. https://doi.org/10.1038/s41586-023-06063-y.