Legumain 是一种溶酶体半胱氨酸蛋白酶，在多种实体瘤高表达，是抗肿瘤靶向药物的理想靶标。大蒜研碎时蒜氨酸与蒜酶相遇产生大蒜辣素，大蒜辣素具有抑制肿瘤细胞生长作用，但不稳定性造成其成药困难。本项目提出将Legumain的抗体与蒜酶偶联，偶联物定向肿瘤后，再给予蒜氨酸，在肿瘤组织与蒜酶原位反应释放大蒜辣素，产生抑制肿瘤生长作用。体外采用Legumain高表达的4T1小鼠乳腺癌细胞，体内采用接种的乳腺癌模型动物，先给予偶联物，再给予蒜氨酸，评价其抗肿瘤活性。同时用荧光标记偶联物评价其靶向性，体外采用激光共聚焦技术评价荧光标记偶联物与肿瘤细胞亲合性，活体动物成像评价荧光标记偶联物在模型小鼠体内的肿瘤靶向性和组织分布。项目提出的Legumain的抗体-蒜酶偶联物与蒜氨酸的前药系统，使得大蒜辣素能在肿瘤组织高度聚集，充分发挥其抗肿瘤活性，为大蒜活性成分高效抗肿瘤药物的研制奠定基础。

The Legumain is a lysosomal proteinase. It has been reported to be overexpressed in the majority of human solid tumors. Legumain should be an ideal candidate anti-tumor target. Allicin, a highly active component from freshly crushed garlic, is the interaction product of alliin with the enzyme alliinase. Allicin was shown to be toxic in various mammalian cells in vitro. But its unstability makes allicin difficult to be a drug alone. We will make use of this cytotoxicity to develop a novel approach to cancer treatment, based on site-directed generation of allicin. Alliinase will be chemically conjugated to a mAb of Legumain directed against a specific tumor. After the mAb-alliinase conjugate is bound to target tumor cells, the substrate, alliin, will be added. In the presence of alliin, tumor-localized alliinase will produce allicin, which should effectively kille tumor cell. In order to asses the targeting of mAb-Allinase conjugate，the confocal laser scanning and noninvasive bioluminescent imaging technologies will be utilized in vitro and in vivo. The mAb-allinase / Alliin prodrug system provide a new approach for developing a high antitumor activity of allicin preparation.