Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer
CD4+ T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC...
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| Language: | English |
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Elsevier
2024-09-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924000778 |
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| author | Joanna Fréderique de Graaf Tamara Pesic Felicia S. Spitzer Koen Oosterhuis Marcel G.M. Camps Iris Zoutendijk Bram Teunisse Wahwah Zhu Tsolere Arakelian Gerben C. Zondag Ramon Arens Jeroen van Bergen Ferry Ossendorp |
| author_facet | Joanna Fréderique de Graaf Tamara Pesic Felicia S. Spitzer Koen Oosterhuis Marcel G.M. Camps Iris Zoutendijk Bram Teunisse Wahwah Zhu Tsolere Arakelian Gerben C. Zondag Ramon Arens Jeroen van Bergen Ferry Ossendorp |
| author_sort | Joanna Fréderique de Graaf |
| collection | DOAJ |
| description | CD4+ T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC-38 colon carcinoma, encoding CD8+ T cell neoantigens alone (noHELP) or in combination with either “universal” helper antigens (uniHELP) or helper neoantigens (neoHELP). Both types of helped vaccines increased the frequency of vaccine-induced CD8+ T cells, and particularly uniHELP increased the fraction of KLRG1+ and PD-1low effector cells. However, when mice were subsequently injected with MC-38 cells, only neoHELP vaccination resulted in significantly better tumor control than noHELP. In contrast to uniHELP, neoHELP-induced tumor control was dependent on the presence of CD4+ T cells, while both vaccines relied on CD8+ T cells. In line with this, neoHELP variants containing wild-type counterparts of the CD4+ or CD8+ T cell neoantigens displayed reduced tumor control. These data indicate that optimal personalized cancer vaccines should include MHC class II-restricted neoantigens to elicit tumor-specific CD4+ T cell help. |
| format | Article |
| id | doaj-art-e92cb4bb786a40a8a8b6b2e207459008 |
| institution | OA Journals |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-e92cb4bb786a40a8a8b6b2e2074590082025-08-20T02:32:49ZengElsevierMolecular Therapy: Oncology2950-32992024-09-0132320083510.1016/j.omton.2024.200835Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancerJoanna Fréderique de Graaf0Tamara Pesic1Felicia S. Spitzer2Koen Oosterhuis3Marcel G.M. Camps4Iris Zoutendijk5Bram Teunisse6Wahwah Zhu7Tsolere Arakelian8Gerben C. Zondag9Ramon Arens10Jeroen van Bergen11Ferry Ossendorp12Immunetune BV, 2333 CH Leiden, the NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsImmunetune BV, 2333 CH Leiden, the NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsSynvolux BV, 2333 CH Leiden, the NetherlandsImmunetune BV, 2333 CH Leiden, the NetherlandsSynvolux BV, 2333 CH Leiden, the NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsImmunetune BV, 2333 CH Leiden, the Netherlands; Synvolux BV, 2333 CH Leiden, the NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, the NetherlandsImmunetune BV, 2333 CH Leiden, the NetherlandsDepartment of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; Corresponding author: Ferry Ossendorp, Department of Immunology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.CD4+ T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC-38 colon carcinoma, encoding CD8+ T cell neoantigens alone (noHELP) or in combination with either “universal” helper antigens (uniHELP) or helper neoantigens (neoHELP). Both types of helped vaccines increased the frequency of vaccine-induced CD8+ T cells, and particularly uniHELP increased the fraction of KLRG1+ and PD-1low effector cells. However, when mice were subsequently injected with MC-38 cells, only neoHELP vaccination resulted in significantly better tumor control than noHELP. In contrast to uniHELP, neoHELP-induced tumor control was dependent on the presence of CD4+ T cells, while both vaccines relied on CD8+ T cells. In line with this, neoHELP variants containing wild-type counterparts of the CD4+ or CD8+ T cell neoantigens displayed reduced tumor control. These data indicate that optimal personalized cancer vaccines should include MHC class II-restricted neoantigens to elicit tumor-specific CD4+ T cell help.http://www.sciencedirect.com/science/article/pii/S2950329924000778MT: Regular IssueDNA vaccinecancer vaccineneoantigenspersonalized medicineimmunotherapy |
| spellingShingle | Joanna Fréderique de Graaf Tamara Pesic Felicia S. Spitzer Koen Oosterhuis Marcel G.M. Camps Iris Zoutendijk Bram Teunisse Wahwah Zhu Tsolere Arakelian Gerben C. Zondag Ramon Arens Jeroen van Bergen Ferry Ossendorp Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer Molecular Therapy: Oncology MT: Regular Issue DNA vaccine cancer vaccine neoantigens personalized medicine immunotherapy |
| title | Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer |
| title_full | Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer |
| title_fullStr | Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer |
| title_full_unstemmed | Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer |
| title_short | Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer |
| title_sort | neoantigen specific t cell help outperforms non specific help in multi antigen dna vaccination against cancer |
| topic | MT: Regular Issue DNA vaccine cancer vaccine neoantigens personalized medicine immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924000778 |
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