細胞激素3(IL-3)為一個調控幹細胞分化與增生的造血因子。先前的研究指出，IL-3修飾過的腫瘤將會減緩它在老鼠體內的生長速率。並且IL-3可以加強細胞毒性T細胞對外生型抗原的辨識，進而抑制轉移的癌細胞。因此利用IL-3作為癌症治療將是一個很有潛力的方式。但是在生物體內大量表現IL-3，將造成嚴重的副作用。因此，在這研究中，將建立一個誘導型的線病毒攜帶細胞激素3的表現系統作為攝護腺癌的基因治療之用。利用BD adenovirus Tet-on 系統為載體將基因帶到腫瘤上，其優點在於基因的表現可以被四環黴素所調控，以降低基因治療的風險；而利用線病毒載體，將可使IL-3大量且局部的表現在腫瘤位置，更有效的去提高對腫瘤的免疫反應。
細胞激素3的表現量取決於四環黴素的濃度。在實驗中，使用了兩種不同的運送系統，將四環黴素運送到目標細胞。實驗結果顯示，利用Alzet osmotic pump 運送藥物比藉由飲用水吸收更有效率。運送效率的不同可以進一步的從腫瘤生長延緩的程度中看出。利用小鼠攝護腺癌模式(TRAMP C-1)去評估IL-3對抑制腫瘤生長的影響，結果顯示IL-3會減緩腫瘤的生長，並增加腫瘤組織內浸潤的免疫細胞，但是所誘導的細胞毒殺反應仍然不足以排除腫瘤，這表示此治療模式應該再結合其他治療方式如放射線治療，以達到最有效的成果。

Interleukin 3 (IL-3) is a hematopoietic factor and can stimulate stem cell proliferation and differentiation. In previous studies, IL-3 transduced tumors grow slower than parental tumors in vivo. Besides, IL3 could enhance CTL generation to exogenous antigen and then suppress metastatic cancer. Therefore, IL-3 gene therapy will be a potential approach for treatment of cancer. However, the large amount of IL-3 expression in host will result in systemic side effect. In this study, I will establish an inducible adenovirus IL-3 gene expression system for prostate cancer therapy. The adenovirus Tet-on system (BD) was used as gene vector to deliver IL-3 gene to tumor cell. The advantage of Tet-on system is that the inserted gene can be regulated by doxycycline (Dox) to reduce the risk of gene therapy. Moreover, the intratumoral expression of IL-3 by adenovirus can concentrate the IL-3 protein inside tumor and was more effective in enhancing the IL-3 elicited tumor-specific cellular immunity.
The expression level of IL-3 depends on the concentration of Dox both in vitro and in vivo. In this study, two procedures were used to deliver Dox to the target in vivo. The results demonstrated that it is more efficient to deliver the Dox by Alzet osmotic pump than by drinking water uptake. This effect was further reflected in a longer tumor growth delay. The antitumor effect of IL-3 was evaluated in a mouse mode of prostate cancer (TRAMP C-1). During the early stage of tumor development, IL-3 treated tumors displayed a slower growth rate compared with control tumors. The expression of IL-3 within tumors increased the amount of tumor-infiltrating lymphocytes (TILs). However, this effect was not able to induce enough CTL response to reject the tumor. It is therefore suggested to combine this system with others, such as radiation therapy, for treatment of prostate cancer.

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