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首页> 外文期刊>Journal of Translational Medicine >Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax? encapsulated CTL/T helper peptides
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Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax? encapsulated CTL/T helper peptides

机译：通过对VacciMax？的单次免疫可以排除老年小鼠中表达HPV-16的大型肿瘤。封装的CTL / T辅助肽

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The incidence of cancer increases significantly in later life, yet few pre-clinical studies of cancer immunotherapy use mice of advanced age. A novel vaccine delivery platform (VacciMax?,VM) is described that encapsulates antigens and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The therapeutic potential of VM-based vaccines administered as a single dose was tested in HLA-A2 transgenic mice of advanced age (48–58 weeks old) bearing large palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations contained a single peptide, a mixture of four peptides or the same four peptides linked together in a single long peptide. All VM formulations contained PADRE and CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil emulsion. VM-formulated vaccines containing the four peptides as a mixture or linked together in one long peptide eradicated 19-day old established tumors within 21 days of immunization. Peptide-specific cytotoxic cellular responses were confirmed by ELISPOT and intracellular staining for IFN-γ producing CD8+ T cells. Mice rendered tumor-free by vaccination were re-challenged in the opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7 expressing tumor cell line. None of these mice developed tumors following the re-challenge. In summary, this report describes a VM-formulated therapeutic vaccine with the following unprecedented outcome: a) eradication of large tumors (> 700 mm3) b) in mice of advanced age c) in less than three weeks post-immunization d) following a single vaccination.
机译：在以后的生活中，癌症的发病率显着增加，但是很少有临床前癌症免疫疗法的研究使用高龄小鼠。描述了一种新型的疫苗递送平台（VacciMax ？，VM），该平台将油包水型乳状液中的抗原和佐剂包裹在多层脂质体内。在患有大型可触及的TC1 / A2肿瘤的高龄（48-58周龄）HLA-A2转基因小鼠中测试了单剂施用基于VM的疫苗的治疗潜力。基于VM的疫苗包含一种或多种具有源自HPV 16 E6和E7的人CTL表位的肽。 VM制剂包含单个肽，四个肽的混合物或在单个长肽中连接在一起的相同四个肽。所有VM配方均包含PADRE和CpG作为佐剂，而ISA51作为油包水乳液的疏水性成分。包含四种肽的混合物或在一个长肽中连接在一起的VM配制疫苗可在免疫21天之内根除19天大的已建立的肿瘤。通过ELISPOT和细胞内染色证实了产生IFN-γ的CD8 + T细胞的肽特异性细胞毒性细胞应答。通过接种使无肿瘤的小鼠在另一侧受到1000万HLF-16肿瘤细胞（另一种表达HLA-A2 / E6 / E7的肿瘤细胞系）的攻击。这些小鼠在再次攻击后均未出现肿瘤。总而言之，本报告描述了一种VM配制的治疗性疫苗，其具有以下前所未有的结果：a）在不到三岁的小鼠中根除大肿瘤（> 700 mm 3 ）b） d）单次疫苗接种后几周。

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