Nuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford, United Kingdom.
Department of BioMedical Research, Immunology RIA, University Hospital of Bern, Bern, Switzerland.
Front Immunol. 2019 May 15;10:1015. doi: 10.3389/fimmu.2019.01015. eCollection 2019.
Personalized cancer vaccines hold promises for future cancer therapy. Targeting neoantigens is perceived as more beneficial compared to germline, non-mutated antigens. However, it is a practical challenge to identify and vaccinate patients with neoantigens. Here we asked whether two neoantigens are sufficient, and whether the addition of germline antigens would enhance the therapeutic efficacy. We developed and used a personalized cancer nano-vaccine platform based on virus-like particles loaded with toll-like receptor ligands. We generated three sets of multi-target vaccines (MTV) to immunize against the aggressive B16F10 murine melanoma: one set based on germline epitopes (GL-MTV) identified by immunopeptidomics, another set based on mutated epitopes (Mutated-MTV) predicted by whole exome sequencing and a last set combines both germline and mutated epitopes (Mix-MTV). Our results demonstrate that both germline and mutated epitopes induced protection but the best therapeutic effect was achieved with the combination of both. Our platform is based on Cu-free click chemistry used for peptide-VLP coupling, thus enabling bedside production of a personalized cancer vaccine, ready for clinical translation.
个体化癌症疫苗有望成为未来癌症治疗的新方法。与种系、未突变的抗原相比，靶向新生抗原被认为更具优势。然而，识别和接种具有新生抗原的患者是一个实际的挑战。在这里，我们想知道是否有两个新生抗原就足够了，以及添加种系抗原是否会增强治疗效果。我们开发并使用了一种基于负载 Toll 样受体配体的病毒样颗粒的个体化癌症纳米疫苗平台。我们生成了三套针对侵袭性 B16F10 鼠黑色素瘤的多靶点疫苗（MTV）：一套基于免疫肽组学鉴定的种系表位（GL-MTV），另一套基于全外显子测序预测的突变表位（Mutated-MTV），还有一套结合了种系和突变表位（Mix-MTV）。我们的结果表明，种系和突变表位都能诱导保护，但两者结合的治疗效果最佳。我们的平台基于无铜点击化学用于肽-VLP 偶联，从而能够在床边生产个体化癌症疫苗，准备进行临床转化。
