Tumor-Homing of Mesenchymal Stem Cells Infected with Oncolytic Virus in a Canine Patient

Abstract

Intravenous administration of oncolytic adenovirus (OAds) can be challenging, although various vehicles for the delivery of the virus to the tumor have been described. The efficacy of mesenchymal stem cells (MSCs) as a virus vehicle has been reported in mouse models and canine and human patients, but the actual action mechanism has never been described in patients. It is of importance to determine whether MSCs infected with OAds can reach the tumor and release the virus in a clinical setting. For this purpose, GFP-labeled MSCs were infected with an OAd and inoculated into a companion dog diagnosed with spontaneous lung carcinoma. Forty-eight hours later, the tumor was excised and analyzed microscopically by flow cytometry for GFP fluorescence detection, and a cellular culture was established. Peripheral blood samples were taken to quantify the oncolytic adenovirus by qRT-PCR. Green fluorescence cells detected in the cellular culture by microscopy and flow cytometry revealed 0.69% GFP-positive cells in the tumor. OAd in peripheral blood was confirmed by qRT-PCR during follow-up. For the first time, the tumoral-homing capacity of OAds infected-MSC has been confirmed in a clinical setting, helping to explain the clinical response mechanism, whose efficacy was previously reported in canine and human patients.

Systemic cellular viroimmunotherapy for canine high-grade gliomas

“…E1A-mutant human Ads demonstrated potent cytolytic effects in human gliomas 42 43 and canine Ads in extracranial solid tumors, either administered intratumorally 13 18 or carried by dMSCs, with higher clinical benefit. 6 Although dCelyvir has been reported to reach an extracranial solid Open access in a canine patient, 44 this is the first time that systemically administered viral treatment has been shown to effectively reach the brain tumor and show biological activity, a fact of vital importance for the efficacy of the therapy. Despite that, the limited efficacy of dCelyvir in treating high-grade gliomas could have been due to (1) the specific characteristics of the immune system in the CNS; (2) the fact that the viral load reaching the tumor was reduced by the bloodbrain barrier; (3) due to the MSC sequestration in the lungs (or other organs); or (4) by the large tumor size at the time of inclusion in the study.…”

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…”

The role of mesenchymal stem cells in cancer and prospects for their use in cancer therapeutics

“…Extensive research is underway exploring the use of MSCs for delivering gene therapeutic agents, chemotherapeutics, and oncolytic viruses (OVs) to achieve precise treatment of malignant tumors, yielding promising outcomes. 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 Table 1 summarizes additional research details in recent years utilizing MSCs as therapeutic carriers to target tumor cells and inhibit tumor development.…”