| First Author | Kr??ger C | Year | 2025 |
| Journal | Cancer Treat Res Commun | Volume | 44 |
| Pages | 100950 | PubMed ID | 40456204 |
| Mgi Jnum | J:386574 | Mgi Id | MGI:8347844 |
| Doi | 10.1016/j.ctarc.2025.100950 | Citation | Kruger C, et al. (2025) Epidermal growth factor receptor specific immunotherapy for SHH medulloblastoma tested in an in vitro blood-brain barrier-model. Cancer Treat Res Commun 44:100950 |
| abstractText | Despite advances in treating pediatric malignant tumors like SHH-medulloblastoma (SHH-MB), the current standard of care remains surgery followed by chemo- and radiotherapy. This aggressive therapy goes along with a significant morbidity with many long-term side effects, especially in children and adolescents. Therefore, more targeted therapies are urgently needed. Immunotoxins (ITs) conjugated to tumor-antigen specific antibodies have shown potential for selectively targeting tumor cells. In this study, we generated a single chain variable fragment (scFv)-based IT that incorporates a truncated, less immunogenic variant of Pseudomonas Exotoxin A (ETA'). The IT specifically targets the epidermal growth factor receptor (EGFR), a tumor-associated antigen commonly overexpressed in SHH-MB. Wecould demonstrate that this immunotherapeutic approach reduces tumor cell viability and induces apoptosis in MB-cell lines with IC(50) values ranging from 3.1 to 17.5 nM. Given that SHH-MB exhibit dysregulated PI3-kinase (PI3K) pathway signaling, we combined the IT with a PI3K inhibitor. Combination treatment led to dose-dependent reductions in IC(50) values (from 2.51 - 13.9 nM at 0.5 microM start concentration to 1.01 - 3.4 nM at 2 microM start concentration). Additionally, we could demonstrate that the generated IT can successfully cross the blood-brain barrier (BBB) in vitro in an in vitro BBB-model based on human brain microvascular endothelial (HBMEC) cells . These results suggest that this immunotherapeutic approach is a promising candidate for further development and clinical application. |
