Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces
Antibody-mediated delivery of immunogenic viral CD8+ T-cell epitopes to redirect virus-specific T cells toward cancer cells is a promising new therapeutic avenue to increase the immunogenicity of tumors. Multiple strategies for viral epitope delivery have been shown to be effective. So far, most of...
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Taylor & Francis Group
2024-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2329321 |
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| author | W. van der Wulp W. Luu M. E. Ressing J. Schuurman S. I. van Kasteren L. Guelen R. C. Hoeben B. Bleijlevens M. H. M. Heemskerk |
| author_facet | W. van der Wulp W. Luu M. E. Ressing J. Schuurman S. I. van Kasteren L. Guelen R. C. Hoeben B. Bleijlevens M. H. M. Heemskerk |
| author_sort | W. van der Wulp |
| collection | DOAJ |
| description | Antibody-mediated delivery of immunogenic viral CD8+ T-cell epitopes to redirect virus-specific T cells toward cancer cells is a promising new therapeutic avenue to increase the immunogenicity of tumors. Multiple strategies for viral epitope delivery have been shown to be effective. So far, most of these have relied on a free C-terminus of the immunogenic epitope for extracellular delivery. Here, we demonstrate that antibody-epitope conjugates (AECs) with genetically fused epitopes to the N-terminus of the antibody can also sensitize tumors for attack by virus-specific CD8+ T cells. AECs carrying epitopes genetically fused at the N-terminus of the light chains of cetuximab and trastuzumab demonstrate an even more efficient delivery of the T-cell epitopes compared to AECs with the epitope fused to the C-terminus of the heavy chain. We demonstrate that this increased efficiency is not caused by the shift in location of the cleavage site from the N- to the C-terminus, but by its increased proximity to the cell surface. We hypothesize that this facilitates more efficient epitope delivery. These findings not only provide additional insights into the mechanism of action of AECs but also broaden the possibilities for genetically fused AECs as an avenue for the redirection of multiple virus-specific T cells toward tumors. |
| format | Article |
| id | doaj-art-c04c265bd991403696916acc78b8076a |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-c04c265bd991403696916acc78b8076a2025-01-31T04:19:38ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2329321Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfacesW. van der Wulp0W. Luu1M. E. Ressing2J. Schuurman3S. I. van Kasteren4L. Guelen5R. C. Hoeben6B. Bleijlevens7M. H. M. Heemskerk8Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The NetherlandsGenmab, Utrecht, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The NetherlandsGenmab, Utrecht, The NetherlandsDivision of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, The NetherlandsGenmab, Utrecht, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The NetherlandsGenmab, Utrecht, The NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, The NetherlandsAntibody-mediated delivery of immunogenic viral CD8+ T-cell epitopes to redirect virus-specific T cells toward cancer cells is a promising new therapeutic avenue to increase the immunogenicity of tumors. Multiple strategies for viral epitope delivery have been shown to be effective. So far, most of these have relied on a free C-terminus of the immunogenic epitope for extracellular delivery. Here, we demonstrate that antibody-epitope conjugates (AECs) with genetically fused epitopes to the N-terminus of the antibody can also sensitize tumors for attack by virus-specific CD8+ T cells. AECs carrying epitopes genetically fused at the N-terminus of the light chains of cetuximab and trastuzumab demonstrate an even more efficient delivery of the T-cell epitopes compared to AECs with the epitope fused to the C-terminus of the heavy chain. We demonstrate that this increased efficiency is not caused by the shift in location of the cleavage site from the N- to the C-terminus, but by its increased proximity to the cell surface. We hypothesize that this facilitates more efficient epitope delivery. These findings not only provide additional insights into the mechanism of action of AECs but also broaden the possibilities for genetically fused AECs as an avenue for the redirection of multiple virus-specific T cells toward tumors.https://www.tandfonline.com/doi/10.1080/19420862.2024.2329321antibody-epitope conjugates (AECs)virus-specific T-cellsimmunotherapyredirecting T-cellsbispecific-antibodies |
| spellingShingle | W. van der Wulp W. Luu M. E. Ressing J. Schuurman S. I. van Kasteren L. Guelen R. C. Hoeben B. Bleijlevens M. H. M. Heemskerk Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces mAbs antibody-epitope conjugates (AECs) virus-specific T-cells immunotherapy redirecting T-cells bispecific-antibodies |
| title | Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces |
| title_full | Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces |
| title_fullStr | Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces |
| title_full_unstemmed | Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces |
| title_short | Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces |
| title_sort | antibody epitope conjugates deliver immunogenic t cell epitopes more efficiently when close to cell surfaces |
| topic | antibody-epitope conjugates (AECs) virus-specific T-cells immunotherapy redirecting T-cells bispecific-antibodies |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2329321 |
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