Kojima Naoya, Biao Le, Nakayama Tomoko, Ishii Mariko, Ikehara Yuzuru, Tsujimura Kunio
Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
J Control Release. 2008 Jul 2;129(1):26-32. doi: 10.1016/j.jconrel.2008.03.023. Epub 2008 Apr 7.
In the present study, the adjuvant capacity of oligomannose-coated liposomes (OMLs) was evaluated in mice, and an OML-based vaccine was shown to induce effective anti-tumor immunity. C57BL/6 mice were immunized subcutaneously with OML-encased ovalbumin (OVA) and challenged with OVA-expressing E.G7-OVA tumor cells. All mice that received OVA in OMLs completely rejected the E.G7-OVA tumor. Spleen cells from the immunized mice showed strong cytotoxic activity against E.G7-OVA cells, but not against the parental EL4 cells. The therapeutic efficacy of OML-encased OVA against established E.G7-OVA tumors was then investigated. When the tumor mass became palpable (8-10 mm in length), the mice were treated with a single injection of 1 microg of OML-encased OVA. Tumor growth was reduced significantly in mice treated with OML-encased OVA and tumors were completely eliminated in about 40% of these mice. Similar results were obtained using EL4 tumors, with the EL4 cell lysate used as an antigen. These results indicate that an OML-based vaccine with an encased tumor antigen might be useful clinically to raise an effective immune response against a tumor.
在本研究中,对寡甘露糖包被脂质体(OML)在小鼠体内的佐剂能力进行了评估,结果显示基于OML的疫苗可诱导有效的抗肿瘤免疫。将C57BL/6小鼠皮下免疫OML包裹的卵清蛋白(OVA),并用表达OVA的E.G7-OVA肿瘤细胞进行攻击。所有接受OML中OVA的小鼠均完全排斥E.G7-OVA肿瘤。免疫小鼠的脾细胞对E.G7-OVA细胞表现出强大的细胞毒活性,但对亲本EL4细胞无此活性。随后研究了OML包裹的OVA对已建立的E.G7-OVA肿瘤的治疗效果。当肿瘤块可触及(长度为8-10毫米)时,给小鼠单次注射1微克OML包裹的OVA进行治疗。用OML包裹的OVA治疗的小鼠肿瘤生长明显减缓,约40%的小鼠肿瘤被完全清除。使用EL4肿瘤并以EL4细胞裂解物作为抗原也获得了类似结果。这些结果表明,一种包裹肿瘤抗原的基于OML的疫苗在临床上可能有助于引发针对肿瘤的有效免疫反应。