In-Silico based design of Lysosome membrane protein 2 targeted multi-epitope vaccine against Breast Cancer

Abstract

Although the clinical therapeutic approaches have improved, breast cancer remains one of the most widespread malignancies on a global scale and remains a major burden on the population's health. In silico approaches to the design of therapeutic cancer vaccines provide an economic and efficient solution to the generation of specific immune responses against cancer-associated antigens. Lysosome-Associated Membrane protein 2 (LAMP2) has been considered in the current study, where it is an antigen with the potential of creating a multi-epitope subunit vaccine targeting breast cancer by using various set of immunoinformatic tools. Amino-acid sequence of LAMP2 was obtained at UniProt database and interrogated to determine B-cell, cytotoxic Tlymphocyte (CTL), and helper T-lymphocyte (HTL) epitopes. Antigenicity, allergenicity, toxicity, and population coverage were rigorously screened on candidate epitopes, which guaranteed not only the vaccine safety but also the wide range of immunogenic efficacy. The chosen epitopes were then modeled and tested in physicochemical characteristics, secondary, tertiary structure, and molecular docking of Toll-like receptors (such as TLR2 and TLR3). Both epitopes were conjugated to the appropriate adjuvants and linker sequences in order to enhance immunogenicity. The computational simulations showed a stable interaction and a strong antigenic response, which means that LAMP2-derived epitopes can induce a strong immune response to breast cancer cells. In general, this in silico investigation demonstrates that LAMP2 can be an excellent immunogenic target and recommends additional refinement and next steps of validation, both in vivo and in vitro.