Summary: | 碩士 === 國立成功大學 === 生物化學研究所 === 98 === Cancer immunotherapy, contrasted with traditional tumor therapy, is a new strategy to give rise to the immune response of patients oneself and destroy the tumor cells without the unwanted side-effects. One of the fast and efficient approaches of cancer immunotherapy is to inhibit the molecules which play a negative role in anti-tumor immunity. Utilizing an established animal model and the RNAi technique, we design a platform to find the potential therapeutic shRNA against negative regulator of dendritic cell by systematic screening. At first, we deliver mixed three shRNA into the abdomen of tumor-bearing mice and observe the tumor curve. The data show that mice treated with clec4a2 shRNA demonstrating the best therapeutic effect and inducing higher cytotoxic activity in lymphocyte. To analyse individual shRNA further, we check clec4a2 shRNA knockdown efficacy and then separately deliver three shRNA to tumor-bearing mice. Observing the tumor curve, mice which treated with clec4a2-1 shRNA and clec4a2-3 shRNA show the better therapeutic effect. To investigate the possible mechanism, the therapeutic effect is caused of enhanced cytotoxic activity in lymphocyte and more CD4+ and CD8+ lymphocyte infiltration in tumor part. Finally, we validate the therapeutic effect by compensating the shRNA-treated mice for clec4a2 gene.
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