Okuno K, Nakamura K, Tanaka A, Yachi K, Yasutomi M
First Department of Surgery, Kinki University School of Medicine, Osaka, Japan.
Surg Today. 1998;28(1):64-9. doi: 10.1007/BF02483610.
To activate hepatic sinusoidal lymphocytes (HSL) and increase the local antitumor activity in the liver, we developed a liver-targeted interleukin-2 (IL-2) compound using a galactose residue-entrapped liposome. We prepared various kinds of IL-2-containing liposomes made by the hydration of powdered dimyristoyl-phosphatidylcholine with aqueous recombinant IL-2 followed by the combination with galactose residues to facilitate the selective uptake by liver parenchymal cells bearing galactose receptors. The IL-2 liposomes were given to C3H/He mice followed by the determination of: (1) organ distribution by 125I-labeled IL-2, (2) antitumor activity of hepatic sinusoidal lymphocytes by 51Cr-release assay, and (3) in vivo antitumor efficacy by the measurement of hepatic metastases. When galactose-entrapped IL-2 liposomes (Gallip-IL-2) were administered, a significantly greater hepatic accumulation of IL-2 was seen for up to 2 weeks compared to IL-2 liposomes or free IL-2. According to these results, the antitumor activity of HSL was significantly augmented. Moreover, when mice with hepatic micrometastases were treated with Gal-lip-IL-2, the area of hepatic metastases was significantly reduced. These findings thus indicate that Gal-lip-IL-2 may enhance the therapeutic efficacy of IL-2 against hepatic metastases and thereby facilitate a more practical daily dosing regimen.
为了激活肝窦淋巴细胞（HSL）并增强肝脏局部抗肿瘤活性，我们利用包载半乳糖残基的脂质体制备了一种肝脏靶向性白细胞介素-2（IL-2）复合物。我们制备了各种含IL-2的脂质体，方法是将二肉豆蔻酰磷脂酰胆碱粉末与重组IL-2水溶液水化，然后与半乳糖残基结合，以促进带有半乳糖受体的肝实质细胞选择性摄取。将IL-2脂质体给予C3H/He小鼠，随后测定：（1）通过125I标记的IL-2确定器官分布；（2）通过51Cr释放试验测定肝窦淋巴细胞的抗肿瘤活性；（3）通过测量肝转移灶来测定体内抗肿瘤疗效。当给予包载半乳糖的IL-2脂质体（Gal-lip-IL-2）时，与IL-2脂质体或游离IL-2相比，在长达2周的时间内观察到IL-2在肝脏中的蓄积显著增加。根据这些结果，HSL的抗肿瘤活性显著增强。此外，当用Gal-lip-IL-2治疗有肝微转移的小鼠时，肝转移灶的面积显著减小。因此，这些发现表明Gal-lip-IL-2可能增强IL-2对肝转移的治疗效果，从而有助于制定更实用的每日给药方案。
