Mesenchymal stem cells as delivery systems for cancer and leukemia gene therapy

• DOI: 10.1200/jco.2004.22.90140.3194
• Publication Date: 2017-04-05T03:17:42Z
• Authors: M. Andreeff; M. Studeny; J. Dembinski; M. Konopleva; R.-Y. Wang; H.-Y. Yang; J. Fueyo; R. E. Champlin; F. Lang; F. C. Marini

3194 Background: We previously demonstrated that intravenously (IV) injected bone marrow-derived mesenchymal stem cells (MSC) integrate into solid tumors as stromal fibroblasts and proliferate selectively in situ. here propose a novel cancer therapy concept based on the intratumoral drug production by gene-modified MSC. Methods: MSC were transduced with adeno (AdV)- or adeno-associated (AAV) virus carrying marker- therapeutic genes. Gene-modified IV mice xenografts. Results: found only tumors, where they not normal tissues. producing human interferon-beta (IFNβ-MSC) directly inhibited growth of metastatic A375 melanoma MDA 231 breast carcinoma following injection (p=0.0073), while recombinant IFNβ protein subcutaneously (SC) did (p=0.14). IFNβ-MSC doubled survival tumor-bearing (p=0.001) SC was ineffective (p=0.021 vs p=0.4). Intraperitoneal (IP) injections ovarian carcinomas their (SKOV-3) cured 70% OVAR-3 mice. IP administration replication competent oncolytic adenovirus prolonged survival. carotid artery (IA) gliomas proliferated gliomas, brain Intratumoral vivo significantly tumor growth. In model chronic myelogenous leukemia blast crisis (KBM5), interferon α (IFNα) produced induced regressions The differentiation-associated gene 7 (MDA7) MSC, preferentially Gleevec resistant KBM5 CML cells. Conclusions: Results suggest grow inhibit leukemias, cancers. Tumor inhibition required spatial proximity to malignant findings proteins replicating have potent anti-tumor effects when situ use tumor-selective delivery systems. No significant financial relationships disclose.