Session: OR35-Neoplasia of Endocrine Tissues
Bench to Bedside
Room 122 (Moscone Center)
In the current study we stably transfected human MSCs with NIS driven by the CCL5 promoter (RANTES-NIS-MSC). Human colon carcinoma cells LS174t were injected into the spleen of nude mice, which resulted in induction of multifocal liver metastases. We investigated distribution and recruitment of RANTES-NIS-MSCs in liver metastases by 123I-scintigraphy and 124I-PET imaging and ex vivoanalyses after systemic tail vein injections of RANTES-NIS-MSCs.
Five days after intrasplenic tumor cell injection 5x105 RANTES-NIS-MSCs were injected via the tail vein three times in four-day-intervals followed by radionuclide application 48h later. 123I-scintigraphy and biodistribution studies as well as 124I-PET imaging revealed active MSC recruitment and CCL5 promoter activation in the multifocal liver lesions in 70% of mice as shown by tumor-selective iodide accumulation. After i.v. injection of wild-type-MSCs no significant iodide accumulation in liver metastases was observed. Immunofluorescence and real-time PCR analyses confirmed selective MSC recruitment and RANTES/CCL5-promoter activation in the stroma of liver metastases, while healthy liver tissue and non-target organs did not show MSC recruitment. Administration of two therapeutic doses of 131I (55.5 MBq) in RANTES-NIS-MSC treated mice resulted in improved survival.
Taken together, our results convincingly demonstrate selective recruitment of MSCs stably expressing NIS driven by the RANTES/CCL5-promoter into liver metastases resulting in induction of tumor-specific iodide accumulation and a therapeutic effect of 131I, opening the exciting prospect of NIS-mediated radionuclide therapy of metastatic cancers after MSC-mediated gene delivery.
Nothing to Disclose: KK, NS, PD, MJW, CZ, GB, HZ, MH, BG, EW, PJN, CS
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