Virus-like particles from rabbit hemorrhagic disease virus can induce an anti-tumor response

Virus-like particles from rabbit hemorrhagic disease virus can induce an anti-tumor response
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DOI:
10.1016/j.vaccine.2008.07.074
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发表时间:
2008-10-03
期刊:
影响因子:
5.5
通讯作者:
Baird, Margaret A.
Baird, Margaret A.
中科院分区:
医学3区
文献类型:
--
作者:
Peacey, Matthew;Wilson, Sarah;Baird, Margaret A.

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表达异源肿瘤抗原的重组病毒样颗粒(VLP)最近被研究用作疫苗。我们将卵清蛋白(OVA)或OVA衍生的CD4(OTII)和CD8(OTI)表位化学缀合至兔出血性疾病病毒(RHDV)VLP。与OVA缀合的VLP能够交叉致敏来自OVA T细胞受体转基因的OT1小鼠的CD8(+)细胞。VLROTI能够在体内诱导比与蛋白质或肽混合的VLP更高的抗原特异性细胞毒性。此外,我们已经表明,在引入肿瘤之前用VLP、OVA或与OTI和OTII肽偶联的VLP接种的那些动物中,小鼠中侵袭性B16.OVA黑素瘤的生长显著延迟。单独的VLROTI和VLP.OTII均不能抑制肿瘤生长。这项工作表明,RHDV VLP为多种疫苗表位提供了一个通用的支架,使抗原的交叉呈递能够引发有效的细胞介导和抗肿瘤反应。(C)2008爱思唯尔有限公司保留所有权利。
Recombinant virus-like particles (VLP) expressing heterologous tumor antigens have recently been investigated for use as vaccines. We have chemically conjugated ovalbumin (OVA) or OVA-derived CD4 (OTII) and CD8 (OTI) epitopes, to rabbit hemorrhagic disease virus (RHDV) VLP. VLP conjugated with OVA were able to cross-prime CD8(+) cells from OT1 mice transgenic for the OVA T cell receptor. VLROTI was able to induce higher antigen-specific cytotoxicity in vivo than VLP mixed with either the protein or the peptide. Furthermore we have shown that the growth of the aggressive B16.OVA melanoma in mice was significantly delayed in those animals that had been vaccinated with VLP.OVA or with VLP coupled with both OTI and OTII peptides prior to the introduction of the tumor. Neither VLROTI nor VLP.OTII alone were capable of inhibiting tumor growth. This work suggests that RHDV VLP offer a versatile scaffold for multiple vaccine epitopes, enabling cross-presentation of the antigen to elicit potent cell-mediated and anti-tumor responses. (C) 2008 Elsevier Ltd. All rights reserved.