Immunoprevention of KRAS-driven lung adenocarcinoma by a multipeptide vaccine
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// Jing Pan 1, * , Qi Zhang 1, * , Shizuko Sei 2 , Robert H. Shoemaker 2 , Ronald A. Lubet 2 , Yian Wang 1 and Ming You 1 1 Cancer Center and Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA 2 Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA * These authors have contributed equally to this work Correspondence to: Ming You, email: myou@mcw.edu Keywords: immunoprevention, KRAS, lung adenocarcinoma, peptide vaccine, MHC class II Received: December 06, 2016 Accepted: March 01, 2017 Published: August 01, 2017 ABSTRACT Lung cancer remains the leading cause of cancer death worldwide. Mutations in KRAS are detected in up to 30% of lung cancer cases. No effective therapies specifically targeting mutant KRAS have been developed. Vaccination against KRAS mutants is one of the venues of active exploration. The present study evaluated both immunogenicity and antitumor efficacy of a newly formulated multipeptide vaccine targeting multiple epitopes of the KRAS molecule. The formulated vaccine contained top four peptides, which elicited the strongest immunologic response and showed 100% sequence homology between human and mouse. The multipeptide KRAS vaccine was tested in an inducible CCSP-TetO-KRAS G12D mouse model, where the vaccine was administered prior to activating the mutant KRAS protein. The KRAS peptide vaccine exhibited striking efficacy, reducing tumor number and tumor burden by >80% when compared with adjuvant alone. Splenocytes collected from vaccinated animals showed a robust immunologic response to the immunizing peptides. Furthermore, in vitro stimulation of these splenocytes by the vaccinated peptides resulted in the secretion of cytokines indicative of Th1 responses but with minimal secretion of Th2-related cytokines. The multipeptide KRAS vaccine was immunogenic and efficacious in the primary prevention of KRAS-induced lung cancer, indicating that the approach potentially can be used to prevent other KRAS-driven cancers, either alone or in combination with other modalities.
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These vaccines are designed to induce antigen-presenting cells to display mutant KRAS, stimulating attacks by cytotoxic T-cells against cancer cells expressing mutant KRAS neoantigen.
“These vaccines are designed to induce antigen-presenting cells to display mutant KRAS, stimulating attacks by cytotoxic T-cells against cancer cells expressing mutant KRAS neoantigen [78,79,80].”
From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [80]
The Discussion says that mutant RAS peptides or antigen-presenting cells loaded with them generated mutant-specific T-cell responses in earlier studies. But this paper’s vaccine was designed around MHC class II peptides and predominantly stimulated CD4 Th1 responses; the Results found no increase in CD8 tumor-infiltrating cells. It therefore does not establish the claimed cytotoxic T-cell attack as the mechanism of this vaccine. (LLM, conf=0.88)
Experimental — accuracy not yet measuredVaccination can train the immune system to attack cells expressing mutant KRAS.
“Vaccination can train the immune system to attack cells expressing mutant KRAS.”
From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [80]
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Self-citation
- Authors
- Pan, J., Zhang, Q., Sei, S., Shoemaker, R. H., Lubet, R. A., Wang, Y., & You, M.
- Affiliations
- Medical College of Wisconsin (US)
- National Cancer Institute (US)
- Corresponding author
- Pan, Jing
- Zhang, Qi
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2017-08-01
- Volume
- 8
- Issue
- 47
- Pages
- 82689-82699
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5669920
- OpenAlex
- W2742077100
- Cited by
- 38
- References
- 37
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 1
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (N01CN2015000037)
- National Cancer Institute (R01CA223804)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- KRAS, lung adenocarcinoma, multipeptide vaccine, cancer immunoprevention, KRAS G12D, MHC class II, epitope mapping, Th1 response, tumor burden reduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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