Neoantigen Vaccine for Pancreatic Cancer: Current Limitations and Targeted Strategies for Enhancing Immune Response

Ziyu Xu; Xinran Zhao

doi:10.54097/7yhm5c60

Authors

Ziyu Xu
Xinran Zhao

DOI:

https://doi.org/10.54097/7yhm5c60

Keywords:

Neoantigen Vaccine, Cancer Vaccine, Immune Response, Pancreatic Cancer

Abstract

Pancreatic cancer is a form of cancer regarded as the most fatal malignant tumor, facing challenges due to its strong invasiveness and limited response to traditional treatment methods. A neoantigen vaccine is a newly developed treatment method that stimulates cytotoxic T-cell response by inducing tumor-specific antigens. Although neoantigen vaccine theoretically possesses advantages of strong individualization and high immunogenicity, their therapeutic effect is limited in pancreatic cancer caused by mechanisms in the tumor microenvironment, physical barriers, immunosuppressive cells, and immune checkpoints, insufficient quantity, and function of APCs, leading to poor antigen presentation. A delivery strategy targeting Mesothelin is believed to enhance antigen presentation and break through immune tolerance due to its characteristic high expression in pancreatic cancer cells. According to the latest clinical trials, only half of the patients showed a T-cell response, suggesting the TME barrier has to be conquered. Based on this result, the delivery system targeting the highly expressed tumor marker Mesothelin significantly enhanced antigen uptake and CD8⁺ T-cell infiltration in the mouse model. This essay focuses on the clinical application limitations and optimization strategies of neoantigen vaccine treatment for pancreatic cancer.

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References

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