Development of dendritic cell loaded MAGE-A2 long peptide; a potential target for tumor-specific T cell-mediated prostate cancer immunotherapy

• Published in: Cancer cell international Vol. 23; no. 1; pp. 1 - 270
• Main Authors: Bakhshi, Parisa, Nourizadeh, Maryam, Sharifi, Laleh, Farajollahi, Mohammad M., Mohsenzadegan, Monireh
• Format: Journal Article
• Language: English
• Published: London BioMed Central 11.11.2023; BMC
• Subjects: Antigens; Cancer immunotherapy; Cancer therapies; CD11c antigen; CD14 antigen; CD40 antigen; CD80 antigen; CD83 antigen; CD86 antigen; Cell division; Cell growth; Cell proliferation; Cytotoxicity; Dendritic cell vaccine; Dendritic cells; Flow cytometry; Immunotherapy; Leukocytes; Long peptide; Lymphocytes; Lymphocytes T; MAGE-A2; Mixed leukocyte reaction; Monoclonal antibodies; Monocytes; Patients; Peptides; Prostate cancer; Proteins; Tumor cells; Tumors; Vaccines; γ-Interferon; United States > US; Germany
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-023-03108-0

Abstract Background Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. Immunotherapy is an emerging treatment modality for cancers that harnesses the immune system’s ability to eliminate tumor cells. In particular, dendritic cell (DC) vaccines, have demonstrated promise in eliciting a tumor-specific immune response. In this study, we investigated the potential of using DCs loaded with the MAGE-A2 long peptide to activate T cell cytotoxicity toward PCa cell lines. Methods Here, we generated DCs from monocytes and thoroughly characterized their phenotypic and functional properties. Then, DCs were pulsed with MAGE-A2 long peptide (LP) as an antigen source, and monitored for their transition from immature to mature DCs by assessing the expression levels of several costimulatory and maturation molecules like CD14, HLA-DR, CD40, CD11c, CD80, CD83, CD86, and CCR7. Furthermore, the ability of MAGE-A2 -LP pulsed DCs to stimulate T cell proliferation in a mixed lymphocyte reaction (MLR) setting and induction of cytotoxic T cells (CTLs) in coculture with autologous T cells were examined. Finally, CTLs were evaluated for their capacity to produce interferon-gamma (IFN-γ) and kill PCa cell lines (PC3 and LNCaP). Results The results demonstrated that the antigen-pulsed DCs exhibited a strong ability to stimulate the expansion of T cells. Moreover, the induced CTLs displayed substantial cytotoxicity against the target cells and exhibited increased IFN-γ production during activation compared to the controls. Conclusions Overall, this innovative approach proved efficacious in targeting PCa cell lines, showcasing its potential as a foundation for the development and improved PCa cancer immunotherapy.