Hombach, Andreas A. and Ambrose, Christine and Lobb, Roy and Rennert, Paul and Abken, Hinrich (2023) A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2<SUP>+</SUP> Solid Cancer. CELLS, 12 (2): 248. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THERAPY; IMMUNORECEPTORS; COSTIMULATION; ACTIVATION; LYMPHOMA; chimeric antigen receptor; ErbB2 (Her2; neu); herceptin; scFv fusion protein; CD19 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Mar 2024 09:59 |
| Last Modified: | 19 Mar 2024 09:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60333 |
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