Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Immunology, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Eur J Cancer. 2020 Apr;129:80-96. doi: 10.1016/j.ejca.2020.01.010. Epub 2020 Mar 4.
The main goal of peptide-based cancer vaccines is to induce the immune system and activation of effective T cell responses against cancerous cells. Nevertheless, the potency of peptide vaccines is insufficient in most of cases and had limited clinical success. Therefore, the optimization of peptide-based cancer vaccine is essential to achieve powerful therapeutic outcomes. One strategy to enhanced potency of peptide vaccines and induce strong immune responses is the preparation of multi-epitope peptide formulation containing both Th- and cytotoxic T lymphocyte-induced responses epitope using suitable delivery system. For this reason, we studied the effect of Dioleoylphosphatidylethanolamine-containing liposomal vaccine composed of a mixture of short peptides AE36 and E75 (HER2/neu-derived peptides) and long multi-epitope peptide E75-AE36 (linkage of short peptides) in combination with a Pan HLA-DR epitope (PADRE) peptide. These formulations were examined using a series of subcutaneously injection to HER-2 TUBO-tumoured mice in prophylactic and therapeutic model. We observed that mice vaccinated with liposomal long peptide in combination with PADRE resulted in the superior induction of CD4 and CD8 T cells responses and significantly enhanced production of IFN-γ compared with liposomal short peptides and non-liposomal peptides formulations. Moreover, liposome-long peptide with PADRE led to the considerable reduction of tumour growth and lifespan induction in mouse model. In conclusion, our study indicated that liposomal formulation containing long multi-epitope peptide E75-AE36 with PADRE could be used as an effective multi-epitope prophylactic/therapeutic vaccine to generate potent antigen-specific CD8 T-cell immune response and may be introduced as a possible candidate peptide vaccine for breast cancer.
基于肽的癌症疫苗的主要目标是诱导免疫系统并激活针对癌细胞的有效 T 细胞反应。然而，在大多数情况下，肽疫苗的效力不足，临床效果有限。因此，优化基于肽的癌症疫苗对于实现强大的治疗效果至关重要。一种增强肽疫苗效力并诱导强烈免疫反应的策略是制备包含 Th 和细胞毒性 T 淋巴细胞诱导反应表位的多表位肽制剂，使用合适的递药系统。出于这个原因，我们研究了含有二油酰基磷脂酰乙醇胺的脂质体疫苗的效果，该疫苗由混合短肽 AE36 和 E75（HER2/neu 衍生肽）和长多表位肽 E75-AE36（短肽连接）组成，与 Pan HLA-DR 表位（PADRE）肽联合使用。这些制剂在预防性和治疗性 HER-2 TUBO 肿瘤小鼠模型中通过一系列皮下注射进行了检查。我们观察到，用脂质体长肽与 PADRE 联合接种的小鼠中，CD4 和 CD8 T 细胞反应的诱导明显优于脂质体短肽和非脂质体肽制剂，并且 IFN-γ 的产生显著增强。此外，脂质体长肽与 PADRE 联合使用可导致肿瘤生长和小鼠模型中的寿命诱导显著减少。总之，我们的研究表明，含有 PADRE 的长多表位肽 E75-AE36 的脂质体制剂可用作有效的多表位预防性/治疗性疫苗，可产生有效的抗原特异性 CD8 T 细胞免疫反应，并可能被引入作为乳腺癌的潜在候选肽疫苗。
