近幾年來以胜肽發展為治療性藥物的研究被許多科學家所重視，眾多的製藥及生技公司對這類藥物的發展也不遺餘力，但僅有少數藥物胜肽被核准上市，因為胜肽藥物仍有許多尚待解決的難題。在過去的研究中發現許多藥物胜肽在人體的生體可用性(bioavailability) 不足，也有些研究顯示了若增加胜肽藥物在血中的半衺期 (half-life) 可以增加生體可用性。本研究主要探討三個不同的藥物胜肽Alloferon、Thymosin-α1及Alloferon-6C在離體 (ex vivo) 及活體動物實驗上的免疫調節功能之差異性，Alloferon與Thymosin-α1這二個藥物胜肽在過去的研究中皆有增進自然殺手細胞 (Natural killer cell) 的活性、增加受病毒感染之小鼠的存活率，及抑制腫瘤細胞生長的能力；而本實驗室所設計的藥物胜肽Alloferon-6C，是將Alloferon的羧基端加上一段六個碳的碳鏈，並探討在免疫調節功能上與Alloferon及Thymosin-α1之差異性。由自然殺手細胞的毒殺力測試發現Alloferon-6C延長了自然殺手細胞的活性，在探討藥物胜肽促進PHA (phytohemagglutinin) 引導小鼠脾臟細胞增生及干擾素 (IFN, interferon) 釋放試驗結果發現Thymosin-α1比Alloferon及Alloferon-6C有更好的效果，最後在評估藥物胜肽佐劑能力 (Adjuvanticity) 的實驗結果得知，高劑量的Alloferon可以促進小鼠周邊血液中抗BSA抗體的合成及增加CD4+及CD8+ T細胞百分比的能力，並且比商品化的佐劑 (Incomplete Freund’s Adjuvant) 有更佳的效果，證實Alloferon具有成為佐劑的能力。

Recently, more and more research of therapeutic drugs based on peptide development was respected by scientists. Pharmaceutical and biotechnological industries had also invested a lot of funds in discovering this kind of drug. However, only a few therapeutic peptides have been approved for clinical application. These disappointing results were not due to the lack of inherent biological potency of the peptide drugs but to the insufficient bioavailability in patients. Some studies promoted the efficacy of peptide drugs by means of increased their half-life in blood.
In this research, we evaluated the modulation of immunological function by three therapeutic peptides, Alloferon, Thymosin-□1 and Allofron-6C. Alloferon and Thymosin-□1 were isolated from insects and bovine thymic hormone. Previous studies indicated that they increased the the cytotoxicity of natural killer (NK) cell, induced the production of interferon, improved the survival rate on mice infected with influenza virus and inhibited the growth of tumors. We designed another therapeutic peptide, Allofron-6C, by adding an acyl chain consist of six carbon units to the carboxyl end of Alloferon.
NK cytotoxicity assay, phytohemagglutinin (PHA) induced T cell proliferation assay, PHA induced interferon (IFN) production assay and adjuvanticity assay were used to examine the immunological function modulated by these therapeutic peptides. The result showed that the cytotoxicity of NK cell was significantly increased after NK cell pre-treated with Alloferon-6C for 4 hours, suggesting that the ex vivo half-life of Alloferon-6C was longer than Alloferon and Thymosin-α1. PHA induced T cell proliferation assay and PHA induced IFN production assay revealed that Thymosin-α1 was the potent one to stimulate T cell proliferation and IFN production. The adjuvanticity assay of therapeutic peptides manifested that high dose of Alloferon could elevate the level of antibody and T cell against BSA in vivo as well as Incomplete Freund’s adjuvant, a commercial adjuvant. Thus, we considered that Alloferon can be used as a new adjuvant.

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