Evaluation of Human Mesenchymal Stromal Cells as Carriers for the Delivery of Oncolytic HAdV-5 to Head and Neck Squamous Cell Carcinomas

Abstract

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.

Emerging delivery strategy for oncolytic virotherapy

“…They demonstrated these MSCs shielded-OA effectively targeted to tumor in many xenografted mouse models after local or systemic administration. 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 A study demonstrated that, after intra-arterial injection, human-derived MSC-loaded OA DNX-2401 can selectively deliver the virus to tumor site of glioma in mice and exert oncolytic effects. 100 Recently, the same team has demonstrated that perfusion-guided endovascular super-selective intra-arterial infusion of MSC-loaded DNX-2401 was safe in humans.…”

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects

“…Lung and pancreatic adenocarcinoma, melanoma IP [161] Men-MSCs + PBMNCs Lung adenocarcinoma, epidermoid carcinoma, pharynx squamous cell carcinoma IP [162] Ad-ICOVIR15, Ad-ICOVIR15-cBITE Men-MSCs Lung adenocarcinoma and epidermoid carcinoma IP [163] Ad-ICOVIR15, Ad-ICOVIR17 AT-MSCs Glioblastoma multiforme IT, IV [164] Ad-ICOCAV17 AT-MSCs Osteosarcoma and brain tumours IV [165] Spontaneous lung carcinoma IV [166] Ad-hOC-E1 BM-MSCs Renal carcinoma IP [167] Ad-RLX-PCDP BM-MSCs Pancreatic cancer IV [168] Ad-Ad5-HexPos3 BM-MSCs, AT-MSCs Head and neck squamous cells carcinoma IV, IP [169] Ad-Ad5-Ki67/IL-15 Source of MSCs non-specified Glioblastoma multiforme IT [170] Ad-5, Ad-3, Ad-5.Pk7-Delta24…”