A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> 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...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/2/248 |
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| author | Andreas A. Hombach Christine Ambrose Roy Lobb Paul Rennert Hinrich Abken |
| author_facet | Andreas A. Hombach Christine Ambrose Roy Lobb Paul Rennert Hinrich Abken |
| author_sort | Andreas A. Hombach |
| collection | DOAJ |
| 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<sup>+</sup> carcinoma. CD19 CAR T cells are redirected towards the ErbB2<sup>+</sup> 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<sup>+</sup> cancer cells and to suppress the ErbB2<sup>+</sup> 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<sup>+</sup> 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. |
| first_indexed | 2024-03-09T13:12:11Z |
| format | Article |
| id | doaj.art-01fa912584b2484ab308bc29215d691d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T13:12:11Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-01fa912584b2484ab308bc29215d691d2023-11-30T21:39:44ZengMDPI AGCells2073-44092023-01-0112224810.3390/cells12020248A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> Solid CancerAndreas A. Hombach0Christine Ambrose1Roy Lobb2Paul Rennert3Hinrich Abken4Department I Internal Medicine, University Hospital Cologne, Robert-Koch-Str. 21, 50931 Köln, GermanyAleta Biotherapeutics Inc., Natick, MA 01760, USAAleta Biotherapeutics Inc., Natick, MA 01760, USAAleta Biotherapeutics Inc., Natick, MA 01760, USALeibniz Institute for Immunotherapy, Division Genetic Immunotherapy, University Regensburg, 93053 Regensburg, GermanyThe 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<sup>+</sup> carcinoma. CD19 CAR T cells are redirected towards the ErbB2<sup>+</sup> 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<sup>+</sup> cancer cells and to suppress the ErbB2<sup>+</sup> 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<sup>+</sup> 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.https://www.mdpi.com/2073-4409/12/2/248chimeric antigen receptorErbB2 (Her2/neu)herceptinscFv fusion proteinCD19 |
| spellingShingle | Andreas A. Hombach Christine Ambrose Roy Lobb Paul Rennert Hinrich Abken A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> Solid Cancer Cells chimeric antigen receptor ErbB2 (Her2/neu) herceptin scFv fusion protein CD19 |
| title | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> Solid Cancer |
| title_full | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> Solid Cancer |
| title_fullStr | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> Solid Cancer |
| title_full_unstemmed | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> Solid Cancer |
| title_short | A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<sup>+</sup> Solid Cancer |
| title_sort | cd19 anti erbb2 scfv engager protein enables cd19 specific car t cells to eradicate erbb2 sup sup solid cancer |
| topic | chimeric antigen receptor ErbB2 (Her2/neu) herceptin scFv fusion protein CD19 |
| url | https://www.mdpi.com/2073-4409/12/2/248 |
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