Interleukin-2/liposomes potentiate immune responses to a soluble protein cancer vaccine in mice
Interleukin-2/liposomes potentiate immune responses to a soluble protein cancer vaccine in mice
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DOI：
10.1007/s00262-005-0013-x
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发表时间：
2006-04-01
影响因子：
5.8
通讯作者：
Bystryn, JC
中科院分区：
文献类型：
--
作者：
Johnston, D;Reynolds, SR;Bystryn, JC
提高癌症疫苗效力的一个关键因素，特别是纯蛋白质或肽抗原，是开发能够强烈但安全地提高其诱导免疫应答能力的程序。在这里，我们描述了将纯蛋白抗原和白细胞介素-2（IL-2）一起封装到脂质体中显著提高免疫应答和肿瘤保护。将C57 B1/6小鼠组每周用皮下注射于PBS中或包封于含有或不含人重组IL-2的脂质体中的约0.1 mg卵清蛋白（OVA）免疫x4次。对照组包括用经辐照的E.G7-OVA细胞（表达卵清蛋白）或PBS免疫的小鼠。在基线和第2周和第4周，通过免疫组收集并合并血清，以通过ELISA测量对OVA的抗体应答。通过ELISPOT测试在第4周获得的脾细胞的抗OVA细胞应答。然后用致死剂量的E.G7-OVA细胞攻击小鼠以测量肿瘤保护性免疫。IL-2脂质体未引起可检测的毒性。与单独或包封在脂质体中而没有IL-2的OVA免疫的小鼠相比，在脂质体中的OVA + IL-2免疫的小鼠中抗体、CD 8（+）T细胞和肿瘤保护性免疫应答显著增强。这些结果表明IL-2脂质体增强了对可溶性蛋白免疫的抗体、细胞和肿瘤保护性免疫应答。这可能提供一种简单、安全和有效的方法来增强由纯蛋白抗原组成的疫苗的免疫原性。
A critical element in improving the potency of cancer vaccines, especially pure protein or peptide antigens, is to develop procedures that can strongly but safely increase their ability to induce immune responses. Here, we describe that encapsulation of a pure protein antigen and interleukin-2 (IL-2) together into liposomes significantly improves immune responses and tumor protection. Groups of C57Bl/6 mice were immunized weekly x4 with -0.1 mg of ovalbumin (OVA) injected subcutaneously in PBS or encapsulated in liposomes with or without human recombinant IL-2. Control groups included mice immunized to irradiated E.G7-OVA cells (that express ovalbumin), or to PBS. Sera were collected and pooled by immunization group at baseline and at weeks 2 and 4 to measure antibody responses to OVA by ELISA. Splenocytes obtained at week 4 were tested for anti-OVA cellular responses by ELISPOT. Mice were then challenged to a lethal dose of E.G7-OVA cells to measure tumor-protective immunity. IL-2 liposomes caused no detectable toxicity. Antibody, CD8(+) T cell, and tumor-protective immune responses were markedly enhanced in mice immunized to OVA + IL-2 in liposomes compared to mice immunized to OVA, either alone or encapsulated into liposomes without IL-2. These results indicate that IL-2 liposomes enhance antibody, cellular, and tumor-protective immune responses to immunization with a soluble protein. This may provide a simple, safe, and effective way to enhance the immunogenicity of vaccines that consist of pure protein antigens.