發展細胞型腫瘤疫苗

開發一個安全的腫瘤疫苗對於臨床應用是相當重要的。先前的研究也已證實將細胞激素混合特定腫瘤抗原可以有效的刺激免疫統對抗腫瘤細胞。然而目前仍有許多的未知的腫瘤抗原，且不同的腫瘤細胞所表現的腫瘤抗原也不同。過去研究也發現直接將細胞激素打入活體內可能造成的嚴重的副作用，因此開發一個安全有效的腫瘤疫苗是相當重要的。為達到此目的，我們將細胞激素直接表現於腫瘤細胞的細胞膜上成為膜式細胞激素，使免疫球細胞在辨認腫瘤抗原時，細胞激素可以直接刺激免疫球細胞，產生對抗腫瘤的能力，甚至達到針對腫瘤的免疫記憶。使用細胞膜表現細胞激素，不會在全身隨處擴散，也增加腫瘤疫苗的安全性。在本研究中我們在腫瘤細胞膜上表現細胞激素為顆粒單核球群落生長因子(GM-CSF)以及(或)介白素18(IL-18)，於活體外我們發現表現膜式細胞激素的腫瘤細胞可以刺激脾臟細胞分裂，另外在Balb/c小鼠皮下植入表現膜式細胞激素的腫瘤細胞，結果我們發現腫瘤同時膜表現GM-CSF與IL-18的組別比個別膜表現的組別有最好的腫瘤疫苗效果。這個結果顯示同時表現GM-CSF與IL-18的膜式細胞激素可以未來可以開發成一個安全的腫瘤疫苗。我們將更進一步的探討其同時表現GM-CSF與IL-18其產生腫瘤疫苗反應的機制。

關鍵字

腫瘤；疫苗；膜表現

並列摘要

The safety of a tumor vaccine is critical for its clinical use. Previous study indicated that the immune system which activated with the combination of two different cytokines retarded tumor growth, but systemic introduction of cytokines could cause strong side effects. To overcome this obstacle, we set up a tumor vaccine with the cytokines anchored on the cell membrane of tumor cells. The simultaneous recognition of tumor antigens and activation by the stimulation with membrane-bound cytokines of immune cells could elicit immune response against tumor cells effectively. In addition, this immune response could develop immune memory and prevent tumor growth. The cytokines would not diffuse arbitrary as the cytokines was anchored on the cell membrane of tumor cells which would be safer than systemic injection. In this study, we used membrane-bound GM-CSF and IL-18 to stimulate splenocytes proliferation in vitro and retarded tumor growth in vivo when these membrane-bound cytokines were injected subcutaneously into the hind limbs of the Balb/c mice. This result implies that the combination of IL-18 and GM-CSF could be used for the prevention of tumor cells and the mechanism of the protective effect could be the new direction for study.

並列關鍵字

tumor ； vaccine ； membrane-bound

參考文獻

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