Enhanced tumor inhibiting effect of 131I-BDI-1-based radioimmunotherapy and cytosine deaminase gene therapy modulated by a radio-sensitive promoter in nude mice bearing bladder cancer

Radioimmunotherapy (RIT) has great potential in cancer therapy. However, its efficacy in numerous tumors is restricted due to myelotoxicity, thereby limiting the dose of radionuclide. To increase tumor radiosensitivity, we incorporated the recombinant lentivirus into the EJ cells (bladder cancer [BC] cells), and examined the combined anti-tumor effects of RIT with I-131-BDI-1(I-131-monoclonal antibody against human BC-1) and gene therapy (GT). The recombinant lentivirus was constructed and packed. The animal xenograft model was built and when the tumor reached about 0.5 cm in diameter, the mice were randomly separated into four groups: (1) RIT + GT: the xenografts were continuously incorporated with the recombinant lentivirus for two days. And 7.4 MBq I-131-BDI-1 was IV-injected, and 10 mg prodrug 5-fluorocytosine (FC) was IV-injected for 7 days, (2) RIT: same dose of I-131-BDI-1 as the previous group mice, (3) GT: same as the first group, except no I-131-BDI-1, and (4) Untreated. Compute tumor volumes in all groups. After 28 days the mice were euthanized and the tumors were extracted and weighed, and the inhibition rate was computed. The RIT + GT mice, followed by the RIT mice, exhibited markedly slower tumor growth, compared to the control mice. The tumor size was comparable between the GT and control mice. The tumor inhibition rates after 28 days of incubation were 42.85 +/- 0.23%, 27.92 +/- 0.21% and 0.57 +/- 0.11% for the four groups, respectively. In conclusion, RIT, combined with GT, suppressed tumor development more effectively than RIT or GT alone. This data highlights the potent additive effect of radioimmune and gene therapeutic interventions against cancer.

Automated summary

Radioimmunotherapy (RIT) combined with gene therapy (GT) has a more effective role in inhibiting tumor development. The results of the study showed that the combination of RIT and GT significantly slowed tumor growth, while RIT or GT alone had no significant effect.