| Autor: |
Stephen Gottschalk, Giedre Krenciute, Heather Tillman, Shondra M. Pruett-Miller, Shaina N. Porter, Jinghui Zhang, Deanna Langfitt, Alejandro Allo Anido, Timothy I. Shaw, Elizabeth Wickman, Jessica Wagner |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2326-6066.c.6550398 |
| Popis: |
Chimeric antigen receptor (CAR) T-cell therapy has had limited success in early-phase clinical studies for solid tumors. Lack of efficacy is most likely multifactorial, including a limited array of targetable antigens. We reasoned that targeting the cancer-specific extra domain B (EDB) splice variant of fibronectin might overcome this limitation because it is abundantly secreted by cancer cells and adheres to their cell surface. In vitro, EDB-CAR T cells recognized and killed EDB-positive tumor cells. In vivo, 1 × 106 EDB-CAR T cells had potent antitumor activity in both subcutaneous and systemic tumor xenograft models, resulting in a significant survival advantage in comparison with control mice. EDB-CAR T cells also targeted the tumor vasculature, as judged by IHC and imaging, and their antivascular activity was dependent on the secretion of EDB by tumor cells. Thus, targeting tumor-specific splice variants such as EDB with CAR T cells is feasible and has the potential to improve the efficacy of CAR T-cell therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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