[Glycosyl-phosphatidylinositol-anchored interleukin-2 expressed on tumor-derived exosomes induces anti-tumor immune response]. 2011

Jia-Mo Zhang, and Xiao-Hou Wu, and Xuan Zhang, and Yao Zhang, and Chun-li Luo
Department of Urology, Yong Chuan Hospital, Chongqing Medical University, Chongqing 402160, China.

OBJECTIVE To prepare IL-2-anchored and tumor-derived exosomes vaccine, and investigate the antitumor efficiency of the special cytotoxic T-lymphocytes induced by Ex/GPI-IL-2. METHODS To construct pEGFP-N1-IL2gpi plasmid coding a fusion gene of a DNA oligo encoding GPI-anchor signal sequence attaching to human IL-2 cDNA. Then T24 cell lines stably expressing GPI-IL-2 proteins (T24/GPI-IL-2) were established. Ex/GPI-IL-2 were isolated and purified by ultrafiltration and sucrose gradient centrifugation, and the morphology and molecule markers were analyzed. The mixed lymphocyte reaction study and cytotoxic study were performed to determine the proliferative effect of T lymphocytes and the cytotoxicity induced by Ex/GPI-IL-2. RESULTS The pEGFP-N1-IL2gpi plasmid was successfully constructed, and cell lines stably expressing GPI-IL-2 fusion proteins were established. Ex/GPI-IL-2 were small vesicular and saucer-shaped in diameter of 30-90 nm, containing heat shock protein 70, intercellular adhesion molecule-1, MAGE-1 and GPI-IL-2. Ex/GPI-IL-2-pulsed could dendritic cells induce proliferation of T cells and cytotoxic immune response more efficiently (P<0.05). CONCLUSIONS GPI-IL-2 gene-modified tumor cells can make the exosomes containing GPI-IL-2 with an increased anti-tumor effect. Our study provides a feasible approach for exosome-based tumor immunotherapy of bladder transitional cell tumors.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D001749 Urinary Bladder Neoplasms Tumors or cancer of the URINARY BLADDER. Bladder Cancer,Bladder Neoplasms,Cancer of Bladder,Bladder Tumors,Cancer of the Bladder,Malignant Tumor of Urinary Bladder,Neoplasms, Bladder,Urinary Bladder Cancer,Bladder Cancers,Bladder Neoplasm,Bladder Tumor,Cancer, Bladder,Cancer, Urinary Bladder,Neoplasm, Bladder,Neoplasm, Urinary Bladder,Tumor, Bladder,Tumors, Bladder,Urinary Bladder Neoplasm
D002295 Carcinoma, Transitional Cell A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS. Carcinomas, Transitional Cell,Cell Carcinoma, Transitional,Cell Carcinomas, Transitional,Transitional Cell Carcinoma,Transitional Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013602 T-Lymphocytes, Cytotoxic Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2. Cell-Mediated Lympholytic Cells,Cytotoxic T Cells,Cytotoxic T Lymphocyte,Cytotoxic T-Lymphocytes,TC1 Cell,TC1 Cells,TC2 Cell,TC2 Cells,Cell Mediated Lympholytic Cells,Cell, Cell-Mediated Lympholytic,Cell, TC1,Cell, TC2,Cell-Mediated Lympholytic Cell,Cytotoxic T Cell,Cytotoxic T Lymphocytes,Cytotoxic T-Lymphocyte,Lymphocyte, Cytotoxic T,Lympholytic Cell, Cell-Mediated,Lympholytic Cells, Cell-Mediated,T Cell, Cytotoxic,T Lymphocyte, Cytotoxic,T Lymphocytes, Cytotoxic,T-Lymphocyte, Cytotoxic
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D017261 Glycosylphosphatidylinositols Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes. GPI Membrane Anchor,GPI Membrane Anchors,Glycosyl-Phosphatidylinositol Membrane Protein Anchor,Glycosylated Phosphatidylinositol,Glycosylphosphatidylinositol Anchor,Glycosylphosphatidylinositol Anchors,Phosphatidylinositol Glycan,Gly-PtdIns,Glycoinositol Phospholipid Membrane Anchor,Glycosyl-Phosphatidylinositol,Glycosyl-Phosphatidylinositol Membrane Protein Anchors,Glycosylated Phosphatidylinositols,Glycosylphosphatidylinositol,Glycosylphosphatidylinositol Linkage,PI-Glycan,Anchor, GPI Membrane,Anchor, Glycosylphosphatidylinositol,Anchors, GPI Membrane,Anchors, Glycosylphosphatidylinositol,Glycan, Phosphatidylinositol,Glycosyl Phosphatidylinositol,Glycosyl Phosphatidylinositol Membrane Protein Anchor,Glycosyl Phosphatidylinositol Membrane Protein Anchors,Linkage, Glycosylphosphatidylinositol,Membrane Anchor, GPI,Membrane Anchors, GPI,PI Glycan,Phosphatidylinositol, Glycosylated,Phosphatidylinositols, Glycosylated
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

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