Abstract
1421
Background: TIM3can regulate T-cell activation is being assessed as target of cancer immunotherapy. However, the applications of TIM3-targeted radioimmunotheray in hepatocellular carcinoma have not been reported yet. Therefore, the aim of this study was to investigate the therapeutic effect with 131I-anti-TIM3 mAb with 5-fluorouracil in HCC mouse model.
Methods: The HCC tumor SMMC7721-GFP xenograft-bearing mice were established and divided into three groups, 5-FU, 5-FU and 131I-anti-TIM3 McAb and control. 5-FU treatment was intraperitoneally injected from Monday to Friday with a therapy break on Saturday and Sunday, and the combination therapy of both 5-FU and 131I-anti-TIM3 McAb. 131I-anti-TIM3 mAb and131I-IgG were prepared, and their biodistribution studies were carried out. The effect of CMRIT on HCC was studied by noninvasive fluorescence imaging and the relative tumor proliferation rate. Results and Discussion: The high expression of TIM3 in HCC tissues were confirmed by RT-PCR, Western blot and whole-body phosphor-autoradiography in vitro or in vivo. Whole-body phosphor-autoradiography also showed higher tumor uptake for 131I-anti-TIM3 mAb vs. 131I-IgG. Biodistribution studies indicated higher tumor accumulation and better T/NT (4.35±0.96) of 131I-anti-TIM3 mAb. Noninvasive fluorescence imaging exhibited a significant tumor growth suppression in the 131I-anti-TIM3 mAb and 5-FU combination therapy group (P<0.01 vs. control; P<0.05 vs.5-FU alone). After treatment with 131I-anti-TIM3 mAb and 5-FU, the tumor growth inhibition rate was up to 65.5± 3.12% in the 131I-anti-TIM3 mAb and 5-FU combination therapy group.
Conclusions: Our study suggested the combination of 131I-anti-TIM3 mAb and 5-FU may be a promising CMRIT strategy for HCC
