Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes.
Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes.
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DOI：
10.3390/molecules21101284
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发表时间：
2016-09-26
期刊：
影响因子：
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通讯作者：
Kono K
中科院分区：
文献类型：
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作者：
Yoshizaki Y;Yuba E;Komatsu T;Udaka K;Harada A;Kono K
为了建立基于多肽疫苗的肿瘤免疫治疗，我们研究了用pH敏感的融合聚合物修饰脂质体包裹抗原肽以诱导抗原特异性免疫的方法。用3-甲基戊二酸化的超支化聚缩水甘油醇修饰卵黄磷脂酰胆碱和L-二油酰磷脂酰乙醇胺，分别与树突状细胞(DC)上的主要组织相容性复合体(β)I和II类分子结合。负载多肽的脂质体被DC有效摄取。这些多肽被输送到他们的细胞质中。携带OVA-I的MGlu-HPG修饰脂质体对荷有OVA表达的E.G7-OVA肿瘤的小鼠，比注射游离OVA-I肽更有效地诱导OVA特异性CTL的激活。小鼠在OVA-I多肽MGlu-HPG脂质体免疫后强烈排斥E.G7-OVA细胞，而用游离OVA-I多肽处理的小鼠仅轻微排斥该细胞。此外，OVA-I多肽脂质体免疫荷瘤小鼠可有效抑制肿瘤体积。OVA-II修饰的MGlu-HPG脂质体免疫小鼠后，肿瘤抑制作用明显减弱。结果表明，MGlu-HPG脂质体可能有助于改进CTL诱导肽，从而有效地进行肿瘤免疫治疗。
To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAPβA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs). The peptide-loaded liposomes were taken up efficiently by DCs. The peptides were delivered into their cytosol. Administration of OVA-I-loaded MGlu-HPG-modified liposomes to mice bearing OVA-expressing E.G7-OVA tumors induced the activation of OVA-specific CTLs much more efficiently than the administration of free OVA-I peptide did. Mice strongly rejected E.G7-OVA cells after immunization with OVA-I peptide-loaded MGlu-HPG liposomes, although mice treated with free OVA-I peptide only slightly rejected the cells. Furthermore, efficient suppression of tumor volume was observed when tumor-bearing mice were immunized with OVA-I-peptide-loaded liposomes. Immunization with OVA-II-loaded MGlu-HPG-modified liposomes exhibited much lower tumor-suppressive effects. Results indicate that MGlu-HPG liposomes might be useful for improvement of CTL-inducing peptides for efficient cancer immunotherapy.
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影响因子：
56.9
作者：
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通讯作者：
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