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A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation

Cancer Gene Therapy volume 31, pages 464–471 (2024)Cite this article

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Abstract

KRAS mutations occur commonly in the lung and can lead to the development of non-small cell lung cancer (NSCLC). While the mutated KRAS protein is a neoantigen, it usually does not generate an effective anti-tumor immune response on mucosal/epithelial surfaces. Despite this, mutated KRAS remains a potential target for immunotherapy since immune targeting of this protein in animal models has been effective at eliminating tumor cells. We attempted to develop a KRAS vaccine using mutated and wild-type KRAS peptides in combination with a nanoemulsion (NE) adjuvant. The efficacy of this approach was tested in an inducible mutant KRAS-mouse lung tumor model. Animals were immunized intranasally using NE with KRAS peptides. These animals had decreased CD4+FoxP3+ T cells in both lymph nodes and spleen. Immunized animals also showed higher IFN-γ and IL-17a levels to mutated KRAS that were produced by CD8+ T cells and enhancement in KRAS-specific Th1 and Th17 responses that persisted for 3 months after the last vaccination. Importantly, the immunized animals had significantly decreased tumor incidence compared to control animals. In conclusion, a mucosal approach to KRAS vaccination demonstrated the ability to induce local KRAS-specific immune responses in the lung and resulted in reduced tumor incidence.

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Fig. 1: Schedule of intranasal admintration of vaccines to mice.
Fig. 2: UPLC analysis showed the presence of intact peptide in the nanoemulsion adjuvant.
Fig. 3: Changes in CD4+ lymphocytes and regulatory T cells cell population with peptide-NE immunization.
Fig. 4: Significantly increased IFN-γ and IL-17 production by peptide-NE vaccinated mice.
Fig. 5: Enhanced IFN-γ and IL-17 production by peptide-NE immunized animals.
Fig. 6: Significantly decreased number of tumors in peptide-NE vaccine-immunized animals.
Fig. 7: Induction of long-lasting antigen-specific immune responses in vaccinated animals.

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Acknowledgements

This study was supported by the Development Therapy Fund from Rogel Cancer Center, University of Michigan, and Michigan Nanotechnology Institute for Medicine & Biological Sciences.

Funding

This study was supported by the Development Therapy Fund from Rogel Cancer Center, University of Michigan, and Michigan Nanotechnology Institute for Medicine & Biological Sciences.

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Authors and Affiliations

  1. Michigan Nanotechnology Institute for Medicine and Biological Sciences, Medical School, University of Michigan, Ann Arbor, MI, 48109, USA

    Su He Wang, Zhengyi Cao, Mohammad Farazuddin, Jesse Chen, Katarzyna W. Janczak, Shengzhuang Tang, Jayme Cannon & James R. Baker Jr

  2. Division of Allergy, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA

    Su He Wang, Mohammad Farazuddin & James R. Baker Jr

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  1. Su He Wang
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Contributions

SHW and JRB were responsible for designing the methodology and writing the manuscript. SHW, ZC, FM and JC were responsible for the investigation. KW, ST and JCH were responsible for data collection and analysis. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Su He Wang.

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The authors declare no competing interests.

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Animal use protocols were approved by the University of Michigan Institutional Animal Care and Use Committee (IACUC).

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Wang, S.H., Cao, Z., Farazuddin, M. et al. A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation. Cancer Gene Ther 31, 464–471 (2024). https://doi.org/10.1038/s41417-023-00717-9

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