In vivo scintigraphic imaging of antitumor effects by combined radioiodine therapy and human sodium iodide symporter gene immunotherapy.
In a previous study, we demonstrated that pcDNA3.1/hNIS (human sodium iodide symporter) vaccination generated hNIS-associated CD8+IFN-gamma+ (interferon-gamma) T cells, which are known to be involved in antitumor immunity. However, the immune response induced was insufficient to control tumor growth in vivo, which required a novel approach to potentiate hNIS vaccination effects. In the present study, we administered 131I radioiodine therapy prior to hNIS vaccination in CT26/hNIS tumor-bearing mice to facilitate the vaccine-induced immune response. We characterized hNIS-associated cytotoxic T-cell immune response and the antitumor effects induced by this 131I + hNIS combination therapy. The survival rates of CT26/hNIS tumor cells were significantly reduced by 131I treatment compared with the parental CT26 cells in vitro. 131I + hNIS combination therapy stably suppressed tumor growth below or near the original tumor size level of initial treatment, achieving 100% survival rates. Specifically, 131I + hNIS therapy enhanced IFN-gamma production, hNIS-associated antitumor cytotoxic T-lymphocyte (CTL) response, and induced more dendritic cells but reduced T-regulatory cells in tumor masses. Collectively, these results suggest that combined therapy effectively enhances hNIS-associated antitumor immune response, leading to CT26/hNIS tumor growth inhibition and complete survival in Balb/C mice. These findings provide a novel and effective means of treating cancer.
Choi
Yun
Y
Departments of Pathology, Tumor Biology, and Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jeon
Yong Hyun
YH
Paik
Jin Ho
JH
Ko
Jinkyung
J
Choi
Dae Han
DH
Chung
June Key
JK
Kim
Chul Woo
CW
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000517:prevention & control / Q000532:radiotherapy / Q000628:therapy*; D011877:Radionuclide Imaging / Q000379:methods; D027981:Symporters / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019444:Vaccines, DNA / Q000627:therapeutic use*; D000099209:Sodium-Iodide Symporters
D019496:Cancer Vaccines; D007457:Iodine Radioisotopes; D027981:Symporters; D019444:Vaccines, DNA; D000099209:Sodium-Iodide Symporters