Modifying Antigen-Encapsulating Liposomes with KALA Facilitates MHC Class I Antigen Presentation and Enhances Anti-tumor Effects.
Modifying Antigen-Encapsulating Liposomes with KALA Facilitates MHC Class I Antigen Presentation and Enhances Anti-tumor Effects.
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DOI：
10.1016/j.ymthe.2017.01.020
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Naoya Miura;H. Akita;Naho Tateshita;Takashi Nakamura;H. Harashima
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文献类型：
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作者：
Naoya Miura;H. Akita;Naho Tateshita;Takashi Nakamura;H. Harashima
对于成功的抗癌疫苗，主要组织相容性复合体 (MHC) I 类抗原呈递是一个要求。为了实现这一点，必须通过克服内体/溶酶体将抗原递送到细胞质。我们之前报道过，用 KALA 肽（WEAKLAKALAKALAKHLAKALAKALKA）（一种 α-螺旋阳离子肽）修饰的脂质纳米颗粒可以将封装的 pDNA 有效地递送至骨髓源性树突状细胞（BMDC）的细胞质。在此，我们报道了使用 KALA 修饰的脂质体作为抗原载体，试图诱导有效的抗原特异性细胞免疫。与用细胞穿透肽八精氨酸 (R8) 修饰的颗粒 (R8-OVA-LPs) 相比，皮下注射 KALA 修饰的卵清蛋白 (OVA) 封装脂质体 (KALA-OVA-LPs) 引发了更有效的 OVA 特异性细胞毒性 T 淋巴细胞活性和抗肿瘤作用。此外，通过 KALA-OVA-LP 免疫，OVA 特异性 CD8+T 细胞的数量有所增加。用 KALA-OVA-LP 处理 BMDC 诱导大量 MHC I 类抗原呈递。此外，KALA-OVA-LP 的酸性 pH 依赖性膜去稳定活性强烈表明它们能够逃离内体/溶酶体，从而将其货物递送至细胞质。总的来说，KALA 修饰的脂质体是一种潜在的抗原递送平台，可用作蛋白质疫苗。
For a successful anti-cancer vaccine, antigen presentation on the major histocompatibility complex (MHC) class I is a requirement. To accomplish this, an antigen must be delivered to the cytoplasm by overcoming the endosome/lysosome. We previously reported that a lipid nanoparticle modified with a KALA peptide (WEAKLAKALAKALAKHLAKALAKALKA), an α-helical cationic peptide, permits the encapsulated pDNA to be efficiently delivered to the cytoplasm in bone marrow-derived dendritic cells (BMDCs). Herein, we report on the use of KALA-modified liposomes as an antigen carrier, in an attempt to induce potent antigen-specific cellular immunity. The subcutaneous injection of KALA-modified ovalbumin (OVA)-encapsulating liposomes (KALA-OVA-LPs) elicited a much more potent OVA-specific cytotoxic T lymphocyte activity and anti-tumor effect in comparison with particles that were modified with octa-arginine (R8), a cell-penetrating peptide (R8-OVA-LPs). In addition, the numbers of OVA-specific CD8+T cells were increased by immunization the KALA-OVA-LPs. The treatment of BMDCs with KALA-OVA-LPs induced a substantial MHC class I antigen presentation. Furthermore, the acidic pH-dependent membrane destabilization activity of KALA-OVA-LPs strongly suggests that they are able to escape from endosomes/lysosomes and thereby deliver their cargos to the cytoplasm. Collectively, the KALA-modified liposome is a potential antigen delivery platform for use as a protein vaccine.