The route of administration dictates the immunogenicity of peptide-based cancer vaccines in mice.
The route of administration dictates the immunogenicity of peptide-based cancer vaccines in mice.
复制标题
给药途径决定了基于肽的癌症疫苗在小鼠中的免疫原性。
DOI：
10.1007/s00262-018-02294-5
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Celis,Esteban
中科院分区：
文献类型：
--
作者：
Sultan,Hussein;Kumai,Takumi;Nagato,Toshihiro;Wu,Juan;Salazar,AndresM;Celis,Esteban
由代表细胞毒性T淋巴细胞（CTL）表位的合成肽组成的疫苗长期以来被认为是治疗癌症的简单且具有成本效益的方法。然而，这些疫苗在临床上对患有可测量疾病的患者的有效性仍然值得怀疑。我们认为，肽疫苗的不良性能是由于它们不能产生足够大的CTL应答，而CTL应答是对已建立的肿瘤产生积极影响所必需的。在临床中引发CTL的肽疫苗通常以与设计用于诱导抗体应答的疫苗相同的方式施用：皮下注射，并且在许多情况下使用弗氏佐剂。我们在这里报告，肽疫苗和聚ICLC佐剂通过非常规的静脉注射免疫途径管理产生实质上更高的CTL反应相比，传统的皮下注射，导致在小鼠中更成功的抗肿瘤作用。此外，两亲性抗原构建体如棕榈酰化肽被证明是比长肽构建体更好的免疫原，长肽构建体现在在临床上流行。目前的研究结果如果转化为临床环境，可能有助于消除广泛存在的对肽疫苗是否能治疗癌症的怀疑。
Vaccines consisting of synthetic peptides representing cytotoxic T-lymphocyte (CTL) epitopes have long been considered as a simple and cost-effective approach to treat cancer. However, the efficacy of these vaccines in the clinic in patients with measurable disease remains questionable. We believe that the poor performance of peptide vaccines is due to their inability to generate sufficiently large CTL responses that are required to have a positive impact against established tumors. Peptide vaccines to elicit CTLs in the clinic have routinely been administered in the same manner as vaccines designed to induce antibody responses: injected subcutaneously and in many instances using Freund’s adjuvant. We report here that peptide vaccines and poly-ICLC adjuvant administered via the unconventional intravenous route of immunization generate substantially higher CTL responses as compared to conventional subcutaneous injections, resulting in more successful antitumor effects in mice. Furthermore, amphiphilic antigen constructs such as palmitoylated peptides were shown to be better immunogens than long peptide constructs, which now are in vogue in the clinic. The present findings if translated into the clinical setting could help dissipate the wide-spread skepticism of whether peptide vaccines will ever work to treat cancer.