K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice
KRAS G12A somatic point mutation in adenocarcinomas is categorized clinically as ineligibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to improve immunogenicity w...
| Main Authors: | , , , , |
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| Format: | Article |
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Multidisciplinary Digital Publishing Institute
2021
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| Online Access: | http://psasir.upm.edu.my/id/eprint/93999/ |
| _version_ | 1848861893854232576 |
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| author | Siak, Pui Yan Wong, Kuan Yee Song, Adelene Ai Lian Abdul Rahim, Raha Lian, Lionel Aun In |
| author_facet | Siak, Pui Yan Wong, Kuan Yee Song, Adelene Ai Lian Abdul Rahim, Raha Lian, Lionel Aun In |
| author_sort | Siak, Pui Yan |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | KRAS G12A somatic point mutation in adenocarcinomas is categorized clinically as ineligibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to improve immunogenicity was developed as a potential vaccine against G12A-mutant KRAS cancers. Additionally, coupling of the 139A epitope with a tetanus toxoid (TTD) universal T-cell epitope to improve antigenicity was also reported. To facilitate convenient oral administration, Lactococcus lactis, which possesses innate immunomodulatory properties, was chosen as a live gastrointestinal delivery vehicle. Recombinant L. lactis strains secreting a G12A mutated K-ras control and 139A with and without TTD fusion were generated for comparative immunogenicity assessment. BALB/c mice were immunized orally, and high survivability of L. lactis passage through the gastrointestinal tract was observed. Elevations in B-cell count with a concomitant titre of antigen-specific IgG and interferon-γ secreting T-cells were observed in the 139A treated mice group. Interestingly, an even higher antigen-specific IgA response and interferon-γ secreting T-cell counts were observed in 139A-TTD mice group upon re-stimulation with the G12A mutated K-ras antigen. Collectively, these results indicated that an antigen-specific immune response was successfully stimulated by 139A-TTD vaccine, and a TTD fusion was successful in further enhancing the immune responses. |
| first_indexed | 2025-11-15T13:08:22Z |
| format | Article |
| id | upm-93999 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T13:08:22Z |
| publishDate | 2021 |
| publisher | Multidisciplinary Digital Publishing Institute |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-939992023-06-15T22:09:02Z http://psasir.upm.edu.my/id/eprint/93999/ K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice Siak, Pui Yan Wong, Kuan Yee Song, Adelene Ai Lian Abdul Rahim, Raha Lian, Lionel Aun In KRAS G12A somatic point mutation in adenocarcinomas is categorized clinically as ineligibility criteria for anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. In this study, a modified G12A-K-ras epitope (139A) with sequence-specific modifications to improve immunogenicity was developed as a potential vaccine against G12A-mutant KRAS cancers. Additionally, coupling of the 139A epitope with a tetanus toxoid (TTD) universal T-cell epitope to improve antigenicity was also reported. To facilitate convenient oral administration, Lactococcus lactis, which possesses innate immunomodulatory properties, was chosen as a live gastrointestinal delivery vehicle. Recombinant L. lactis strains secreting a G12A mutated K-ras control and 139A with and without TTD fusion were generated for comparative immunogenicity assessment. BALB/c mice were immunized orally, and high survivability of L. lactis passage through the gastrointestinal tract was observed. Elevations in B-cell count with a concomitant titre of antigen-specific IgG and interferon-γ secreting T-cells were observed in the 139A treated mice group. Interestingly, an even higher antigen-specific IgA response and interferon-γ secreting T-cell counts were observed in 139A-TTD mice group upon re-stimulation with the G12A mutated K-ras antigen. Collectively, these results indicated that an antigen-specific immune response was successfully stimulated by 139A-TTD vaccine, and a TTD fusion was successful in further enhancing the immune responses. Multidisciplinary Digital Publishing Institute 2021 Article PeerReviewed Siak, Pui Yan and Wong, Kuan Yee and Song, Adelene Ai Lian and Abdul Rahim, Raha and Lian, Lionel Aun In (2021) K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice. Vaccines, 9 (3). art. no. 195. pp. 1-18. ISSN 2076-393X https://www.mdpi.com/2076-393X/9/3/195 10.3390/vaccines9030195 |
| spellingShingle | Siak, Pui Yan Wong, Kuan Yee Song, Adelene Ai Lian Abdul Rahim, Raha Lian, Lionel Aun In K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice |
| title | K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice |
| title_full | K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice |
| title_fullStr | K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice |
| title_full_unstemmed | K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice |
| title_short | K-ras peptide mimotope induces antigen specific Th1 and B-cell immune responses against G12A-mutated K-Ras antigen in balb/c mice |
| title_sort | k-ras peptide mimotope induces antigen specific th1 and b-cell immune responses against g12a-mutated k-ras antigen in balb/c mice |
| url | http://psasir.upm.edu.my/id/eprint/93999/ http://psasir.upm.edu.my/id/eprint/93999/ http://psasir.upm.edu.my/id/eprint/93999/ |