Efficient Eradication of Established Tumors in Mice with Cationic Liposome-Based Synthetic Long-Peptide Vaccines
Efficient Eradication of Established Tumors in Mice with Cationic Liposome-Based Synthetic Long-Peptide Vaccines
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DOI：
10.1158/2326-6066.cir-16-0283
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发表时间：
2017-03-01
影响因子：
10.1
通讯作者：
Ossendorp, Ferry
中科院分区：
文献类型：
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作者：
Varypataki, Eleni Maria;Benne, Naomi;Ossendorp, Ferry
用合成长肽（SLP）进行治疗性疫苗接种可以在临床上有效地对抗HPV诱导的癌前病变;然而，它们在已建立的恶性病变中的效率仍有改进的余地。在这里，我们报告了高的治疗效力的阳离子脂质体装载明确定义的肿瘤特异性SLP和TLR 3配体作为佐剂。平均粒径为160 nm的阳离子颗粒可强烈激活功能性、抗原特异性的CD 8（+）和CD 4（+）T细胞，并在皮内接种后诱导针对靶细胞的体内细胞毒性。在低剂量（1 nmol）的SLP下，我们的脂质体制剂在两个独立模型（黑色素瘤和HPV诱导的肿瘤）中显着控制了肿瘤生长，甚至治愈了75%-100%的小鼠大型肿瘤。治愈的小鼠被完全保护免于以其他致死剂量的肿瘤细胞进行第二次攻击，这表明脂质体SLP在配制用于癌症免疫治疗的强大疫苗中的潜力。(C)2017年AACR。
Therapeutic vaccination with synthetic long peptides (SLP) can be clinically effective against HPV-induced premalignant lesions; however, their efficiency in established malignant lesions leaves room for improvement. Here, we report the high therapeutic potency of cationic liposomes loaded with well-defined tumor-specific SLPs and a TLR3 ligand as adjuvant. The cationic particles, with an average size of 160 nm, could strongly activate functional, antigen-specific CD8(+) and CD4(+) T cells and induced in vivo cytotoxicity against target cells after intradermal vaccination. At a low dose (1 nmol) of SLP, our liposomal formulations significantly controlled tumor outgrowth in two independent models (melanoma and HPV-induced tumors) and even cured 75%-100% of mice of their large established tumors. Cured mice were fully protected from a second challenge with an otherwise lethal dose of tumor cells, indicating the potential of liposomal SLP in the formulation of powerful vaccines for cancer immunotherapy. (C) 2017 AACR.