Abstract
HER2/neu is an immunogenic protein inducing both humoral and cell-mediated immune responses. The antigen-specific cytotoxic T lymphocytes (CTLs) are the main effector immune cells in the anti-tumor immunity. To induce an effective CTL specific response against P5+435 single peptide derived from rat HER2/neu oncogene, we used a liposome delivery vehicle. In vivo enhancement of liposome stability and intracytoplasmic delivery of peptides are the main strategies which elevate the liposome-mediated drug delivery. Liposomes containing high transition temperature phospholipids, such as DSPC, are stable with prolonged in vivo circulation and more accessibility to the immune system. Incorporation of DOPE phospholipid results in the effective delivery of peptide into the cytoplasm via the endocytotic pathway. To this end, the P5+435 peptide was linked to Maleimide-PEG2000-DSPE and coupled on the surface of nanoliposomes containing DSPC: DSPG: Cholesterol with/without DOPE. We observed that mice vaccinated with Lip-DOPE-P5+435 formulation had the highest number of IFN-γ- producing CTLs with the highest cytotoxic activity that consequently led to significantly smallest tumor size and prolonged survival rate in the TUBO mice model. In conclusion, our study indicated that the liposomal form of P5+435 peptide containing DOPE can be regarded as a promising prophylactic anti-cancer vaccine to generate potent antigen-specific immunity.
Highlights
Since the discovery of tumor-associated antigens (TAAs) in the 1990s, various immunotherapy approaches, such as peptide vaccines, have been developed for cancer treatment [1]
The present study aimed to evaluate the immunogenicity of liposome-linked P5+435 peptide, an in-silico designed multiepitope long peptide consisting of two CD8+ T cells epitopes, P5 and P435, attached to the surface of liposome nanoparticles
From the liposomal point of view, our results show that the formulations of the peptide with high transition temperature liposomes -with or without DOPE- significantly enhance the T cell cytotoxic activity over the free peptide, suggesting the role of this form of liposomal formulation in eliciting Cytotoxic T lymphocyte (CTL) responses
Summary
Since the discovery of tumor-associated antigens (TAAs) in the 1990s, various immunotherapy approaches, such as peptide vaccines, have been developed for cancer treatment [1]. Sufficient uptake, processing, and the presentation of antigenic peptides by activated antigen-presenting cells (APCs) via MHC-I as well as efficient activation of effector cells exert a critical role in promoting an effective anti-tumor immunity [9]. In this regard, to improve the efficiency of peptide vaccines, different approaches including the design of the specific antigenic peptides, application of appropriate antigen delivery systems, and potent adjuvants have been investigated [10,11,12,13]
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