Human sodium iodide symporter gene adjunctive radiotherapy to enhance the preventive effect of hMUC1 DNA vaccine.
We demonstrate the use of combination therapy to overcome the limitations of cancer DNA vaccines by adding radioiodine gene therapy in an animal cancer model. We established a stable cell line (CT26/hMUC1-hNIS-Fluc: CMNF) expressing the hMUC1, hNIS and Fluc genes using a retro- and lentivirus system. The survival rates (%) of CMNF cells were determined using clonogenic assays after (131)I treatment. After i.m. immunization to 4 groups of Balb/c mice (pcDNA3.1, pcDNA3.1+(131)I, pcDNA3-hMUC1+PBS and pcDNA3-hMUC1+(131)I groups) with pcDNA3-hMUC1 or pcDNA3.1 once a week for 2 weeks, 1 x 10(5) CMNF cells were injected s.c. into the right thighs of mice in each group. Twenty-one days after tumor transplantation, (131)I was administered i.p. to the pcDNA3.1+(131)I and pcDNA3-hMUC1+ (131)I groups. Tumor progression was monitored in the 4 groups by bioluminescent and scintigraphic imaging and by taking caliper measurements. Tumor masses were extracted and weighted at 39 days post-tumor challenge. We confirmed that CMNF cells highly express hMUC1, hNIS and Fluc by FACS, (125)I uptake, and luciferase assay. The survival rates of CMNF were markedly reduced to (14.6 +/- 1.5)% after (131)I treatment compared with the survival rates of parental cells (p < 0.001). Tumor growth inhibition was significant only in the pcDNA3-hMUC1+ (131)I group at 39 days post challenge. Tumor masses in pcDNA3-hMUC1+ (131)I group were smaller than those of the other groups. This study shows that the weak preventive effects of cancer DNA vaccine can be overcome by radioiodine gene therapy utilizing sodium iodide symporter.
Jeon
Yong Hyun
YH
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Choi
Yun
Y
Kim
Hyun Joo
HJ
Kim
Chul Woo
CW
Jeong
Jae Min
JM
Lee
Dong Soo
DS
Chung
June-Key
JK
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007114:Immunization / Q000379:methods*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D011878:Radiotherapy / Q000379:methods*; D016019:Survival Analysis; D027981:Symporters / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014055:Tomography, Emission-Computed; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D008156:Luciferases; D018396:Mucin-1; D027981:Symporters; D019444:Vaccines, DNA; D000099209:Sodium-Iodide Symporters; C060192:MUC1 protein, human