Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells
<b>Background/Objectives</b>:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PA...
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MDPI AG
2025-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/6/629 |
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| author | Ricardo A. León-Letelier Alejandro M. Sevillano-Mantas Yihui Chen Soyoung Park Jody Vykoukal Johannes F. Fahrmann Edwin J. Ostrin Candace Garrett Rongzhang Dou Yining Cai Fu-Chung Hsiao Jennifer B. Dennison Eduardo Vilar Banu K. Arun Samir Hanash Hiroyuki Katayama |
| author_facet | Ricardo A. León-Letelier Alejandro M. Sevillano-Mantas Yihui Chen Soyoung Park Jody Vykoukal Johannes F. Fahrmann Edwin J. Ostrin Candace Garrett Rongzhang Dou Yining Cai Fu-Chung Hsiao Jennifer B. Dennison Eduardo Vilar Banu K. Arun Samir Hanash Hiroyuki Katayama |
| author_sort | Ricardo A. León-Letelier |
| collection | DOAJ |
| description | <b>Background/Objectives</b>:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting antigenicity. <b>Methods</b>: Here, we show the workflow of designing citrullinated enolase 1 (citENO1) vaccine peptides identified from breast cancer cells by mass spectrometry and demonstrate TNBC vaccine efficacy in the mouse model. Immunized mice with citENO1 peptides or the corresponding unmodified peptides, plus Poly I:C as an adjuvant, were orthotopically implanted with a TNBC murine cell line. <b>Results</b>: Vaccination with citENO1, but not unmodified ENO1 (umENO1), induced a greater percentage of activated CD8+ PD-1+ T cells and effector memory T cells in skin-draining lymph nodes (SDLNs). Remarkably, the citENO1 vaccine delayed tumor growth and prolonged overall survival, which was further enhanced by PD-1 blockade. <b>Conclusions</b>: Our data suggest that cancer-restricted post-translational modifications provide a source of vaccines that induce an anti-cancer immune response. |
| format | Article |
| id | doaj-art-ef0b1319a8e5451ab6bfce9cbe543baa |
| institution | OA Journals |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-ef0b1319a8e5451ab6bfce9cbe543baa2025-08-20T02:21:58ZengMDPI AGVaccines2076-393X2025-06-0113662910.3390/vaccines13060629Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer CellsRicardo A. León-Letelier0Alejandro M. Sevillano-Mantas1Yihui Chen2Soyoung Park3Jody Vykoukal4Johannes F. Fahrmann5Edwin J. Ostrin6Candace Garrett7Rongzhang Dou8Yining Cai9Fu-Chung Hsiao10Jennifer B. Dennison11Eduardo Vilar12Banu K. Arun13Samir Hanash14Hiroyuki Katayama15Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA<b>Background/Objectives</b>:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting antigenicity. <b>Methods</b>: Here, we show the workflow of designing citrullinated enolase 1 (citENO1) vaccine peptides identified from breast cancer cells by mass spectrometry and demonstrate TNBC vaccine efficacy in the mouse model. Immunized mice with citENO1 peptides or the corresponding unmodified peptides, plus Poly I:C as an adjuvant, were orthotopically implanted with a TNBC murine cell line. <b>Results</b>: Vaccination with citENO1, but not unmodified ENO1 (umENO1), induced a greater percentage of activated CD8+ PD-1+ T cells and effector memory T cells in skin-draining lymph nodes (SDLNs). Remarkably, the citENO1 vaccine delayed tumor growth and prolonged overall survival, which was further enhanced by PD-1 blockade. <b>Conclusions</b>: Our data suggest that cancer-restricted post-translational modifications provide a source of vaccines that induce an anti-cancer immune response.https://www.mdpi.com/2076-393X/13/6/629cancer vaccinepost-translational modificationimmunopeptidometriple-negative breast cancerPD-1 blockade |
| spellingShingle | Ricardo A. León-Letelier Alejandro M. Sevillano-Mantas Yihui Chen Soyoung Park Jody Vykoukal Johannes F. Fahrmann Edwin J. Ostrin Candace Garrett Rongzhang Dou Yining Cai Fu-Chung Hsiao Jennifer B. Dennison Eduardo Vilar Banu K. Arun Samir Hanash Hiroyuki Katayama Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells Vaccines cancer vaccine post-translational modification immunopeptidome triple-negative breast cancer PD-1 blockade |
| title | Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells |
| title_full | Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells |
| title_fullStr | Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells |
| title_full_unstemmed | Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells |
| title_short | Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells |
| title_sort | citrullinated eno1 vaccine enhances pd 1 blockade in mice implanted with murine triple negative breast cancer cells |
| topic | cancer vaccine post-translational modification immunopeptidome triple-negative breast cancer PD-1 blockade |
| url | https://www.mdpi.com/2076-393X/13/6/629 |
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