Induction of antigen-specific cytotoxic T-cell response by dendritic cells generated from ecto-mesenchymal stem cells infected with an adenovirus containing the MAGE-D4a gene

Abstract

Abstract. The present study aimed to investigate the feasibility of using ecto-mesenchymal stem cell (EMSC)-derived dendritic cells (DCs) for glioma immunotherapy following infection by a recombinant adenovirus containing the melanoma-associated antigen D4a (MAGE-D4a) gene. The ex vivo cultured EMSCs were infected by the adenoviral plasmid containing MAGE-D4a (pAd/MAGE-D4a). Efficiency of transfection was evaluated through the detection of green fluorescent protein-marked MAGE-D4a. The MAGE-EMSCs were induced to differentiate into DCs, termed as MAGE-EMSCs-DCs. The morphology was subsequently analyzed under a microscope, and methyl thiazolyl tetrazolium (MTT) and interferon-γ (IFN-γ) assays were performed to analyze the cytotoxicity of the MAGE-EMSC-DCs on the human glioma U251 cell line. Following purification by magnetic-activated cell sorting, the EMSCs grew into swirls, with a long spindle shape and were fibroblast-like. The gene transfected with recombinant adenovirus vectors maintained high and stable expression levels of MAGE-D4a, and its efficiency was increased in a multiplicity of infection-dependent manner. The results of the MTT assay indicated that the T cells, primed by the recombinant MAGE-D4a-infected EMSC-DCs in vitro, recognized MAGE-D4a-expressing tumor cell lines in a human leukocyte antigen class I-restricted manner, and evoked a higher cytotoxic T cell (CTL) response. The CTL response induced by the MAGE-EMSC-DCs, co-cultured with the U251 cells for 24 h, produced 765.0 pg/ml IFN-γ, which was significantly greater when compared to the control wells. T lymphocytes stimulated by MAGE-EMSC-DCs evoke a higher CTL response to human glioma cell lines, and may serve as a promising therapeutic modality for the treatment of MAGE-D4a-expressing glioma.

A Novel Angiogenesis-Related Prognostic Signature Associated with the Hepatocellular Carcinoma Immune Microenvironment and Survival Outcome

“…The activation of cytotoxic T lymphocyte responses by DCs is essential for tumor eradication. 41 However, in our study, we did not find an association between high risk score and the proportion of CD8+ T cells. This result may be due to the impaired antigen-presenting function in high-risk populations or the high infiltration of macrophages and Treg cells in the stroma to inhibit T cells, which downregulates the anti-tumor immune response.…”

Induction of cytotoxic effector cells towards cholangiocellular, pancreatic, and colorectal tumor cells by activation of the immune checkpoint CD40/CD40L on dendritic cells

“…Activating the immune checkpoint CD40/CD40L leads to DC maturation, stimulates Th1 immunity, and enables M2 to M1 macrophage differentiation [ 24 ]. Adenoviral vectors increase transgene expression of DC [ 30 , 31 ]. We used CD40L-coding adenoviral vectors to achieve a high expression of CD40L (membrane bound and soluble).…”

Rational design of Polymeric Hybrid Micelles to Overcome Lymphatic and Intracellular Delivery Barriers in Cancer Immunotherapy

“…DCs process and present tumor antigens on their surface via MHC-I molecules 4 , 5 . Upon activation and maturation, antigen-presenting DCs activate an antigen-specific cytotoxic T lymphocyte (CTL) response, which is important for tumor eradication 6 . An efficient CTL response depends on optimal antigen loading and activation of DCs 7 .…”