Personalized Cancer Vaccines Are the Future of Cancer Treatment. Here’s How They Work

Personalized Cancer Vaccines Are the Future of Cancer Treatment. Here’s How They Work

Personalized Cancer Vaccines Are the Future of Cancer Treatment. Here’s How They Work …C0NTINUE READING HERE >>>

Key Takeaways
Cancer vaccine research has advanced to the point where scientists are able to target a patient’s own neoantigens, creating a highly individualized treatment.Personalized neoantigen cancer vaccine platforms are varied, with each offering pros and cons.Only one personalized cancer vaccine has been FDA-approved so far, but the positive results seen in current trials suggest we may see more in the near future.

As cancer continues to vary widely in both characteristics and course from person to person, researchers are focusing on ways to individualize treatment. One notable advancement is the emergence of the personalized cancer vaccine, tailored specifically to each patient’s unique disease profile.

Unlike traditional vaccines that stave off infection, personalized cancer vaccines, also called neoantigen vaccines, are used in people already diagnosed with cancer. The vaccines work by targeting proteins on a tumor called neoantigens. These proteins, which occur only in cancer cells, are the result of genetic mutations and are unique to a specific patient.

“Neoantigens are derived from tumor-specific mutations,” Toni Choueiri, MD, an oncologist at Boston’s Dana-Farber Cancer Institute who is involved in the creation of personalized vaccines for renal cell carcinoma, told Verywell. “We are sure that these are specific to the tumor, and we make a vaccine that is quite specific.”

How is this specificity possible? Scientists rely on genome sequencing, a process that examines human cell components such as DNA and RNA that undergo alterations when someone has cancer. This analysis allows researchers to use a portion of a tumor or a blood sample to get information about the underlying biological processes that cause cancer.

Genome sequencing can be paired with epitope mapping for even greater success. Epitope mapping entails zeroing in on the tiny part of the antigen on the cancer cell known as the epitope, to which antibodies bind in their efforts to remove the offending cell from the body. This pinpointing makes it much easier for scientists to create a vaccine that takes aim at damaged cells while avoiding harming healthy cells, an issue often seen with traditional cancer treatments such as chemotherapy and radiation.

While the scientific community has been working on cancer vaccines for more than five decades, it’s only recently that the tide has turned to precision targeting of tumor cells.

Researchers have been able to scale up personalized cancer vaccine trials thanks to the advent of what Choueiri calls “fast, cheap, available sequencing.” He explained that it now takes weeks to create a vaccine, not months, thanks to advances in sequencing. The cost of sequencing is also declining, he said, which should make it easier to produce vaccines on a larger scale.

All personalized cancer vaccines are designed to provide a customized course of treatment, but they don’t all operate on the same platforms. Some vaccines are protein-based, such as peptide- or epitope-based vaccines, while others are cell-based, virus-based, or rely on RNA technology.

According to Choueiri, there are pros and cons to each type of vaccine platform:

Cell-based vaccines have a high likelihood of eliciting an immune system response but are expensive and difficult to produce. Protein- and peptide-based vaccines are easier to produce and have low toxicity but are quite costly. Viral-based vaccines are simple to manufacture but have the potential to leave a patient vulnerable to infection.RNA-based vaccines offer easy delivery of multiple antigens but are possibly less likely to get a response from the immune system. Additionally, they require special frozen storage.

While personalized neoantigen vaccines are a promising development in treating patients with various types of cancers, it’s important to note that they will not replace traditional cancer treatments. The vaccine is just one tool in the arsenal, Siqing Fu, MD, PhD, a professor in the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center in Houston, told Verywell.

“Cancer is not just one defect. You really need to use everything,” he said.

Currently, only one personalized cancer vaccine has been approved by the Food and Drug Administration (FDA) for use in the United States: Provenge (sipuleucel-T) for prostate cancer. Specifically, this cell-based vaccine is designed for use in patients with metastasized prostate cancer who have few symptoms and whose cancer has not responded to testosterone-lowering therapies.

However, the landscape looks promising for future FDA approvals of personalized cancer vaccines. Below is a sampling of vaccine candidates currently in trials. (Please note that this is not an exhaustive list.)

Melanoma

V940: Novel individualized neoantigen vaccine V940 (also known as mRNA-4157) has been tested in conjunction with targeted therapy drug pembrolizumab in patients with high-risk stage IIIB/IV melanoma that’s been completely resected (removed). Phase 2 trials found that the use of this combination therapy reduced the chance of death or cancer recurrence by 49%; phase 3 trials are ongoing.EVX-01: Peptide-based vaccine EVX-01 plus targeted therapy drug pembrolizumab shows promise for people with metastatic melanoma. Results from phase 1 and 2A trials revealed that two-thirds of patients responded clinically to this combination.EVX-02: In people whose melanoma has been fully removed but who are at high risk of disease recurrence, the DNA-based vaccine EVX-02 combined with the immunotherapy drug nivolumab resulted in long-lasting T-cell responses and relapse-free survival after 12 months.

Pancreatic Cancer

Autogene cevumeran: This mRNA vaccine, currently in phase 2 trials, gives people with pancreatic cancer a needed boost. Phase 1 trials bundled the mRNA vaccine targeting up to 20 neoantigens with the immunotherapy drug atezolizumab and chemotherapy. This regimen was successful in generating a durable T-cell response.

Non-Small Cell Lung Cancer

Tedopi: Tedopi yielded positive results in a phase 3 trial evaluating it against chemotherapy in patients with the biomarker HLA-A2 who have non-small cell lung cancer. The epitope-based vaccine works by taking aim at five tumor-associated neoantigens.

Ovarian Cancer

UPCC 19809 and UPCC 29810: These two vaccine candidates for ovarian cancer, currently in phase 1 and 2 trials, both utilize proteins obtained from a patient’s tumor cells. In the UPCC 19809 trial, the protein is paired with cells created from a patient’s blood, then combined with bevacizumab, a drug that blocks new blood vessel growth. In the UPCC 29810 trial, the protein is injected into the dermis (just under the outermost layer of skin), sometimes combined with Ampligen (rintatolimod), a therapeutic product with a variety of immunogenic and antiviral properties.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Cancer Research Institute. Immunotherapy: cancer vaccines.

Biswas N, Chakrabarti S, Padul V, Jones LD, Ashili S. Designing neoantigen cancer vaccines, trials, and outcomes. Front Immunol. 2023;14:1105420. doi:10.3389/fimmu.2023.1105420

Memorial Sloan Kettering Cancer Center. Next-generation tumor genetic testing.

Backert L, Kohlbacher O. Immunoinformatics and epitope prediction in the age of genomic medicine. Genome Med. 2015;7:119. doi:10.1186/s13073-015-0245-0

Cheever MA, Higano CS. Provenge (sipuleucel-t) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res. 2011;17(11):3520-3526. doi:10.1158/1078-0432.CCR-10-3126

Weber JS, Khattak MA, Carlino MS, et al. Individualized neoantigen therapy mRNA-4157 (V940) plus pembrolizumab in resected melanoma: 3-year update from the mRNA-4157-P201 (KEYNOTE-942) trial. J Clin Oncol. 2024;42(17_suppl):LBA9512-LBA9512. doi:10.1200/JCO.2024.42.17_suppl.LBA9512

Mørk SK, Skadborg SK, Albieri B, et al. Final results: dose escalation study of a personalized peptide-based neoantigen vaccine in patients with metastatic melanoma. J Clin Oncol. 2023;41(16_suppl). doi:10.1200/JCO.2023.41.16_suppl.955

Kleine-Kohlbrecher D, Viborg N, Pavlidis MA, et al. 623 AI-designed personalized neoantigen vaccine, EVX-02, induces robust T-cell responses in melanoma patients. J Immunother Cancer. 2023;11(suppl 1):A1–A1731. doi:10.1136/jitc-2023-SITC2023.0623

Balachandran VP, Rojas LA, Sethna Z, et al. Phase I trial of adjuvant autogene cevumeran, an individualized mRNA neoantigen vaccine, for pancreatic ductal adenocarcinoma. J Clin Oncol. 2022;40(16_suppl):2516-2516. doi:10.1200/JCO.2022.40.16_suppl.2516

Felip E, Besse B, Dziadziuszko R, et al. ATALANTE-1 randomized phase III trial, OSE-2101 versus standard treatment as second or third-line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients. Ann Oncol. 2019;30(suppl 5):v658. doi:10.1093/annonc/mdz260.114

Penn Medicine. Penn ovarian cancer research center immunotherapy program.

By Laurie Saloman

Saloman is a New Jersey-based health writer with more than two decades of experience. She holds a master’s degree in journalism from Northwestern University.

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