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A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer
The efficacy of CD19-specific CAR T cells in the treatment of leukemia/lymphoma relies, at least in part, on the unique properties of the particular CAR and the presence of healthy B cells that enhance the target cell lysis and cytokine secretion through repetitive stimulation. Here, we report to ap...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856536/ https://www.ncbi.nlm.nih.gov/pubmed/36672182 http://dx.doi.org/10.3390/cells12020248 |
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author | Hombach, Andreas A. Ambrose, Christine Lobb, Roy Rennert, Paul Abken, Hinrich |
author_facet | Hombach, Andreas A. Ambrose, Christine Lobb, Roy Rennert, Paul Abken, Hinrich |
author_sort | Hombach, Andreas A. |
collection | PubMed |
description | The efficacy of CD19-specific CAR T cells in the treatment of leukemia/lymphoma relies, at least in part, on the unique properties of the particular CAR and the presence of healthy B cells that enhance the target cell lysis and cytokine secretion through repetitive stimulation. Here, we report to apply the same CAR to target solid tumors, such as ErbB2(+) carcinoma. CD19 CAR T cells are redirected towards the ErbB2(+) cells by a fusion protein that is composed of the herceptin-derived anti-ErbB2 scFv 4D5 linked to the CD19 exodomain. The CD19-4D5scFv engager enabled CD19 CAR T cells to recognize the ErbB2(+) cancer cells and to suppress the ErbB2(+) tumor growth. The primary killing capacity by the ErbB2-redirected CD19 CAR T cells was as efficient as by the ErbB2 CAR T cells, however, adding CD19(+) B cells furthermore reinforced the activation of the CD19 CAR T cells, thereby improving the anti-tumor activities. The ErbB2-redirected CD19 CAR T cells, moreover, showed a 100-fold superior selectivity in targeting cancer cells versus healthy fibroblasts, which was not the case for the ErbB2 CAR T cells. The data demonstrate that the CD19 CAR T cells can be high-jacked by a CD19-scFv engager protein to attack specifically solid cancer, thereby expanding their application beyond the B cell malignancies. |
format | Online Article Text |
id | pubmed-9856536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98565362023-01-21 A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer Hombach, Andreas A. Ambrose, Christine Lobb, Roy Rennert, Paul Abken, Hinrich Cells Article The efficacy of CD19-specific CAR T cells in the treatment of leukemia/lymphoma relies, at least in part, on the unique properties of the particular CAR and the presence of healthy B cells that enhance the target cell lysis and cytokine secretion through repetitive stimulation. Here, we report to apply the same CAR to target solid tumors, such as ErbB2(+) carcinoma. CD19 CAR T cells are redirected towards the ErbB2(+) cells by a fusion protein that is composed of the herceptin-derived anti-ErbB2 scFv 4D5 linked to the CD19 exodomain. The CD19-4D5scFv engager enabled CD19 CAR T cells to recognize the ErbB2(+) cancer cells and to suppress the ErbB2(+) tumor growth. The primary killing capacity by the ErbB2-redirected CD19 CAR T cells was as efficient as by the ErbB2 CAR T cells, however, adding CD19(+) B cells furthermore reinforced the activation of the CD19 CAR T cells, thereby improving the anti-tumor activities. The ErbB2-redirected CD19 CAR T cells, moreover, showed a 100-fold superior selectivity in targeting cancer cells versus healthy fibroblasts, which was not the case for the ErbB2 CAR T cells. The data demonstrate that the CD19 CAR T cells can be high-jacked by a CD19-scFv engager protein to attack specifically solid cancer, thereby expanding their application beyond the B cell malignancies. MDPI 2023-01-07 /pmc/articles/PMC9856536/ /pubmed/36672182 http://dx.doi.org/10.3390/cells12020248 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hombach, Andreas A. Ambrose, Christine Lobb, Roy Rennert, Paul Abken, Hinrich A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer |
title | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer |
title_full | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer |
title_fullStr | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer |
title_full_unstemmed | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer |
title_short | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2(+) Solid Cancer |
title_sort | cd19-anti-erbb2 scfv engager protein enables cd19-specific car t cells to eradicate erbb2(+) solid cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856536/ https://www.ncbi.nlm.nih.gov/pubmed/36672182 http://dx.doi.org/10.3390/cells12020248 |
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