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Engineered Lactococcus lactis biovaccine containing NY-ESO-1 long peptides as potent immunotherapeutics

Year: 2025

Type: article

Abstract: Peptide vaccines have potential for tumour immunotherapy but face challenges in clinical trials, such as human leukocyte antigen limitations, potential cytotoxic T lymphocyte tolerance, short T-cell response duration, weak immune response, and other issues. Optimizing the antigens of peptide vaccines and selecting an effective delivery system are crucial for enhancing their antitumour effects. 3 multiepitope long peptides (NLP) targeting the NY-ESO-1 antigen were screened using bioinformatics methods. An engineered Lactococcus lactis strain (FOLactis) expressing FMS-like tyrosine kinase 3 ligand and the costimulator OX40 ligand was previously developed to activate immune cells. In this study, FOLactis was utilized as a biological carrier for NLP via Mg 2+ -based metal-organic frameworks to stimulate innate and adaptive immunity. The FOL-M@NLP were characterized, and various tumour models were established to assess the antitumour efficacy of the biovaccine. The preliminary mechanism of the immune effect induced by FOL-M@NLP was studied both in vivo and in vitro . The biovaccine FOL-M@NLP was effectively taken up by antigen-presenting cells (APCs). APCs were activated, activating the T-cell response. When FOL-M@NLP was administered subcutaneously in vivo , their antitumour activity was superior to that of NLP and FOLactis alone. The biovaccine improved the immune infiltrating state of the tumour microenvironment and metastasis niche, inhibited tumor progression and prevented recurrence. It is demonstrated that FOL-M@NLP serves as a potent and safe antitumour platform that enhances antigen peptide delivery and facilitates the advancement of therapeutic biological vaccine platforms. • Long peptides screened from the NY-ESO-1 protein contain multiple epitopes with affinity for human and mouse major histocompatibility complexes Ⅰ and Ⅱ. • The biovaccine FOL-M@NLP can be effectively taken up by antigen-presenting cells (APCs), then matures APCs and activates T lymphocytes in vitro. • FOL-M@NLP effectively displays marked anti-tumour or preventive efficacy in various tumour models, enhance the expansion of immune cells in immune organs, improved the immune infiltrating state in tumours and activates innate and adaptive immune response adequately. • The application of FOL-M@NLP induces specific cytotoxicity against target cells expressing NY-ESO-1 and exhibits favourable safety profiles.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2025.102440