| Autor: |
Nilson R; Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany., Krutzke L; Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany., Wienen F; Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany., Rojewski M; Institute for Transfusion Medicine, University Medical Center Ulm, 89081 Ulm, Germany.; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Donation Service, 89081 Ulm, Germany., Zeplin PH; Schlosspark Klinik Ludwigsburg, Privatklinik für Plastische und Ästhetische Chirurgie, 71638 Ludwigsburg, Germany., Funk W; Schönheitsklinik Dr. Funk, 81739 München, Germany., Schrezenmeier H; Institute for Transfusion Medicine, University Medical Center Ulm, 89081 Ulm, Germany.; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Donation Service, 89081 Ulm, Germany., Kochanek S; Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany., Kritzinger A; Department of Gene Therapy, University Medical Center Ulm, 89081 Ulm, Germany. |
| Abstrakt: |
Human multipotent mesenchymal stromal cells (hMSCs) are of significant therapeutic interest due to their ability to deliver oncolytic adenoviruses to tumors. This approach is also investigated for targeting head and neck squamous cell carcinomas (HNSCCs). HAdV-5-HexPos3, a recently reported capsid-modified vector based on human adenovirus type 5 (HAdV-5), showed strongly improved infection of both hMSCs and the HNSCC cell line UM-SCC-11B. Given that, we generated life cycle-unmodified and -modified replication-competent HAdV-5-HexPos3 vector variants and analyzed their replication within bone marrow- and adipose tissue-derived hMSCs. Efficient replication was detected for both life cycle-unmodified and -modified vectors. Moreover, we analyzed the migration of vector-carrying hMSCs toward different HNSCCs. Although migration of hMSCs to HNSCC cell lines was confirmed in vitro, no homing of hMSCs to HNSCC xenografts was observed in vivo in mice and in ovo in a chorioallantoic membrane model. Taken together, our data suggest that HAdV-5-HexPos3 is a potent candidate for hMSC-based oncolytic therapy of HNSCCs. However, it also emphasizes the importance of generating optimized in vivo models for the evaluation of hMSC as carrier cells. |
