Human sodium iodide symporter (hNIS)-mediated radioiodine gene therapy modulates phenotype of cancer cell and enhances the killing activity of cytotoxic T cells in a mouse tumor model

Objectives We examined whether hNIS radioiodine gene therapy can modulate the phenotype of cancer cell, and enhance the killing activity of cytotoxic T cells (CTLs) in mouse tumor model.

Methods 75, 300, 600, 1200, 2400 μCi of I-131 were treated to CT26/hNIS and CT26 cells, and then the number of MHC class I and Fas expressing cells was determined using FACS. Tumor bearing mice were treated with 1200 μCi of I-131, and then the percentage of MHC class I and Fas expressing tumor cells was analyzed using FACS. The number of tumor infiltrating CD8+IFNγ+ and CD11c+CD86+cells, as well as CTLs killing, was confirmed in CT26/hNIS tumor bearing mice treated with PBS or 1200 μCi of I-131 using FACS and LDH analysis, respectively.

Results MHC class I and Fas gene expression was markedly up-regulated in CT26/hNIS but not CT26 in an I-131 dose-dependent manner. Also, MHC class I and Fas expressing cells increased 4.5- and 2.1- fold in CT26/hNIS vs. CT26, respectively. The number of tumor cells infiltrating CD8+IFNγ+ and CD11c+CD86+ increased 5- and 2.5- fold in I-131 vs. PBS, respectively. Also, CTLs assay showed significantly increased specific lysis in I-131 vs. PBS.

Conclusions Our data suggest that phenotypic modification of cancer cells with hNIS radioiodine gene therapy could be used as an attractive therapeutic method to generate tumor-associated immunity in tumor microenvironments.