Intratumoral IL-7 delivery by mesenchymal stromal cells potentiates IFNγ-transduced tumor cell immunotherapy of experimental glioma

Abstract 

The present study reports regression of pre-established experimental rat gliomas as a result of combining peripheral immunization using interferon gamma (IFNγ) transduced autologous tumor cells with local intratumoral delivery of interleukin 7 (IL-7) by mesenchymal stromal cells. IL-7 alone significantly decreased the tumor area and this effect was enhanced with IFNγ immunization. A higher density of intratumoral T-cells was observed in animals receiving combined therapies compared to rats receiving either cytokine alone suggesting that the therapeutic effect is dependent on a T-cell response.

Abbreviations: AEC, 3-amino-9-ethylcarbazole, α-MEM, alpha minimum essential medium, ELISA, enzyme-linked immunosorbent assay, FBS, fetal bovine serum, GBM, glioblastoma multiforme, GFP, green fluorescent protein, HPRT, hypoxanthine phosphoribosyltransferase, HTX, Mayer's Hematoxylin, IFNγ, interferon gamma, IL-7, interleukin 7, i.p., intraperitoneal, i.t., intratumoral, MNP, mononuclear phagocyte, MSC, multipotent mesenchymal stromal cell, RT-PCR, reverse transcriptase polymerase chain reaction, PBS, phosphate buffered saline, TCR, T-cell receptor

Keywords: Glioma, Rats, Mesenchymal stem cells, Interleukin-7, Interferon gamma, Immunotherapy