Mp63-19 Immunogenicity Investigation on Recombinant Bcg Containing Ny-eso-1 Upon Vaccination
Year: 2019
Type: article
Abstract: INTRODUCTION AND OBJECTIVES: Although Mycobacterium bovis Bacillus Calmette-Gu erin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure and unwanted side effects.Here, we generated genetically modified BCG strains with improved immunotherapeutic effects by adding genes that confer evasion of AMPs.METHODS: We constructed recombinant BCG (rBCG) strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human a-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs.Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation.Then, the efficacy of the rBCGs was tested in a growth inhibition assay using two bladder cancer cell lines (5637, T24).RESULTS: We confirmed the presence of cDNA segments corresponding to the Sic and dltA genes in total mRNA of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA), and these rBCGs showed higher survival against AMPs.The growth inhibitory effects of rBCGs on bladder cancer cells were significantly enhanced compared to those of the parent BCG, and THP-1 migration also increased.After 8 h of infection, the levels of internalization were higher in rBCG-infected bladder cancer cells than in BCG-infected cells, and cells infected with rBCGs showed increased release of antitumor cytokines, such as IL-6/12, TNF-a, and INF-g, resulting in inhibition of bacterial killing and immune modulation via antimicrobial peptides.CONCLUSIONS: rBCG-Sic and rBCG-dltA can effectively evade BCG-stimulated AMPs may be significantly improved immunotherapeutic tools to treat bladder cancer.
Source: The Journal of Urology
Authors: Haibo Shen*, Chen Wang, Yingying Chen, Jingman Wang, Ying Wang, ShangHai
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Chung-Ang University
OpenAlex ID: W2942319586