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，并且临床成功率有限。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。提高肽疫苗效力和诱导强免疫应答的一种策略是使用合适的递送系统制备同时包含Th和细胞毒性T淋巴细胞诱导的抗原决定簇的多表位肽制剂。为此原因，我们研究了由短肽AE36和E75（HER2 / neu衍生肽）和长多表位肽E75-AE36（短肽的连接）与Pan HLA-组合组成的含二油酰基磷脂酰乙醇胺的脂质体疫苗的作用DR表位（PADRE）肽。使用一系列的HER-2皮下注射检查了这些制剂⁺ TUBO肿瘤小鼠的预防和治疗模型。我们观察到，与脂质体短肽和非脂质体肽制剂相比，接种脂质体长肽与PADRE组合的小鼠可导致CD4 ⁺和CD8 ⁺ T细胞应答的优异诱导，并显着增强IFN-γ的产生。此外，带有PADRE的脂质体长肽在小鼠模型中导致肿瘤生长和寿命诱导的显着降低。总之，我们的研究表明，含有长多表位肽E75-AE36和PADRE的脂质体制剂可以用作有效的多表位预防/治疗疫苗，以产生有效的抗原特异性CD8 ⁺ T细胞免疫反应，可能作为乳腺癌的候选候选肽疫苗引入。