A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation
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 p...
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| Veröffentlicht in: | Cancer gene therapy 2024-03, Vol.31 (3), p.464-471 |
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| creator | Wang, Su He Cao, Zhengyi Farazuddin, Mohammad Chen, Jesse Janczak, Katarzyna W. Tang, Shengzhuang Cannon, Jayme Baker, James R. |
| description | 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. |
| doi_str_mv | 10.1038/s41417-023-00717-9 |
| format | Article |
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+
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.</description><identifier>ISSN: 0929-1903</identifier><identifier>EISSN: 1476-5500</identifier><identifier>DOI: 10.1038/s41417-023-00717-9</identifier><identifier>PMID: 38177307</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13/21 ; 13/31 ; 13/51 ; 631/1647/350/354 ; 631/67/1059/2325 ; 64/110 ; 64/60 ; Adjuvants ; Animal models ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - therapy ; CD4 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes ; Disease Models, Animal ; Foxp3 protein ; Gene Expression ; Gene Therapy ; Helper cells ; Immune response ; Immunization ; Immunomodulation ; Immunotherapy ; K-Ras protein ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - prevention & control ; Lymph nodes ; Lymphocytes T ; Mice ; Mucosal immunity ; Mutation ; Neoantigens ; Non-small cell lung carcinoma ; Peptides ; Peptides - genetics ; Protein Subunit Vaccines ; Proto-Oncogene Proteins p21(ras) - genetics ; Small cell lung carcinoma ; Tumor cells ; Tumor microenvironment ; Tumors ; Vaccines ; γ-Interferon</subject><ispartof>Cancer gene therapy, 2024-03, Vol.31 (3), p.464-471</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Nature America, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-50e1a0364af503b11ca4e69fd951cafbfa08ca55837868fcd989af7a958d82303</citedby><cites>FETCH-LOGICAL-c375t-50e1a0364af503b11ca4e69fd951cafbfa08ca55837868fcd989af7a958d82303</cites><orcidid>0000-0002-9763-6544 ; 0000-0003-3317-9206</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41417-023-00717-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41417-023-00717-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38177307$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Su He</creatorcontrib><creatorcontrib>Cao, Zhengyi</creatorcontrib><creatorcontrib>Farazuddin, Mohammad</creatorcontrib><creatorcontrib>Chen, Jesse</creatorcontrib><creatorcontrib>Janczak, Katarzyna W.</creatorcontrib><creatorcontrib>Tang, Shengzhuang</creatorcontrib><creatorcontrib>Cannon, Jayme</creatorcontrib><creatorcontrib>Baker, James R.</creatorcontrib><title>A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation</title><title>Cancer gene therapy</title><addtitle>Cancer Gene Ther</addtitle><addtitle>Cancer Gene Ther</addtitle><description>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.</description><subject>13/21</subject><subject>13/31</subject><subject>13/51</subject><subject>631/1647/350/354</subject><subject>631/67/1059/2325</subject><subject>64/110</subject><subject>64/60</subject><subject>Adjuvants</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Disease Models, Animal</subject><subject>Foxp3 protein</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Helper cells</subject><subject>Immune response</subject><subject>Immunization</subject><subject>Immunomodulation</subject><subject>Immunotherapy</subject><subject>K-Ras protein</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - prevention & control</subject><subject>Lymph nodes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mucosal immunity</subject><subject>Mutation</subject><subject>Neoantigens</subject><subject>Non-small cell lung carcinoma</subject><subject>Peptides</subject><subject>Peptides - genetics</subject><subject>Protein Subunit Vaccines</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Small cell lung carcinoma</subject><subject>Tumor cells</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><subject>Vaccines</subject><subject>γ-Interferon</subject><issn>0929-1903</issn><issn>1476-5500</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFP3DAQhS1U1F22_QMckKVeekkZx3FsH1crCqhIlaA99GTNOg54lTiLnSzi39d0KUgcuNhPet-8GT1Cjhl8Y8DVaapYxWQBJS8AZFb6gMxZJetCCIAPZA661AXTwGfkKKUNQDYl_0hmXLEsQM7JnyUNw8511IcxYsCEHd267egbR3dorQ8uW3d-7ceUyVCkHruOWpefbgq31GKwLtIHP97RH9fLG9pPI45-CJ_IYYtdcp-f_wX5_f3s1-qiuPp5frlaXhWWSzEWAhxD4HWFrQC-Zsxi5WrdNlpk2a5bBGVRCMWlqlVrG600thK1UI0qOfAF-brP3cbhfnJpNL1PT_dhcMOUTKlLpcu64lVGv7xBN8MUQ74uU6LWkvO6zFS5p2wcUoquNdvoe4yPhoF5Kt7size5ePOveKPz0Mlz9LTuXfMy8r_pDPA9kLIVbl183f1O7F-nE417</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Wang, Su He</creator><creator>Cao, Zhengyi</creator><creator>Farazuddin, Mohammad</creator><creator>Chen, Jesse</creator><creator>Janczak, Katarzyna W.</creator><creator>Tang, Shengzhuang</creator><creator>Cannon, Jayme</creator><creator>Baker, James R.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9763-6544</orcidid><orcidid>https://orcid.org/0000-0003-3317-9206</orcidid></search><sort><creationdate>20240301</creationdate><title>A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation</title><author>Wang, Su He ; Cao, Zhengyi ; Farazuddin, Mohammad ; Chen, Jesse ; Janczak, Katarzyna W. ; Tang, Shengzhuang ; Cannon, Jayme ; Baker, James R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-50e1a0364af503b11ca4e69fd951cafbfa08ca55837868fcd989af7a958d82303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>13/21</topic><topic>13/31</topic><topic>13/51</topic><topic>631/1647/350/354</topic><topic>631/67/1059/2325</topic><topic>64/110</topic><topic>64/60</topic><topic>Adjuvants</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes</topic><topic>Disease Models, Animal</topic><topic>Foxp3 protein</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Helper cells</topic><topic>Immune response</topic><topic>Immunization</topic><topic>Immunomodulation</topic><topic>Immunotherapy</topic><topic>K-Ras protein</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - prevention & control</topic><topic>Lymph nodes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mucosal immunity</topic><topic>Mutation</topic><topic>Neoantigens</topic><topic>Non-small cell lung carcinoma</topic><topic>Peptides</topic><topic>Peptides - genetics</topic><topic>Protein Subunit Vaccines</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Small cell lung carcinoma</topic><topic>Tumor cells</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><topic>Vaccines</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Su He</creatorcontrib><creatorcontrib>Cao, Zhengyi</creatorcontrib><creatorcontrib>Farazuddin, Mohammad</creatorcontrib><creatorcontrib>Chen, Jesse</creatorcontrib><creatorcontrib>Janczak, Katarzyna W.</creatorcontrib><creatorcontrib>Tang, Shengzhuang</creatorcontrib><creatorcontrib>Cannon, Jayme</creatorcontrib><creatorcontrib>Baker, James R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Su He</au><au>Cao, Zhengyi</au><au>Farazuddin, Mohammad</au><au>Chen, Jesse</au><au>Janczak, Katarzyna W.</au><au>Tang, Shengzhuang</au><au>Cannon, Jayme</au><au>Baker, James R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation</atitle><jtitle>Cancer gene therapy</jtitle><stitle>Cancer Gene Ther</stitle><addtitle>Cancer Gene Ther</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>31</volume><issue>3</issue><spage>464</spage><epage>471</epage><pages>464-471</pages><issn>0929-1903</issn><eissn>1476-5500</eissn><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.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>38177307</pmid><doi>10.1038/s41417-023-00717-9</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-9763-6544</orcidid><orcidid>https://orcid.org/0000-0003-3317-9206</orcidid></addata></record> |
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| ispartof | Cancer gene therapy, 2024-03, Vol.31 (3), p.464-471 |
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| subjects | 13/21 13/31 13/51 631/1647/350/354 631/67/1059/2325 64/110 64/60 Adjuvants Animal models Animals Biomedical and Life Sciences Biomedicine Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - therapy CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes Disease Models, Animal Foxp3 protein Gene Expression Gene Therapy Helper cells Immune response Immunization Immunomodulation Immunotherapy K-Ras protein Lung cancer Lung Neoplasms - genetics Lung Neoplasms - prevention & control Lymph nodes Lymphocytes T Mice Mucosal immunity Mutation Neoantigens Non-small cell lung carcinoma Peptides Peptides - genetics Protein Subunit Vaccines Proto-Oncogene Proteins p21(ras) - genetics Small cell lung carcinoma Tumor cells Tumor microenvironment Tumors Vaccines γ-Interferon |
| title | A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation |
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