PMID- 24322180 OWN - NLM STAT- MEDLINE DCOM- 20140325 LR - 20211021 IS - 1432-1335 (Electronic) IS - 0171-5216 (Linking) VI - 140 IP - 2 DP - 2014 Feb TI - Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene. PG - 281-9 LID - 10.1007/s00432-013-1552-8 [doi] AB - PURPOSE: Melanoma antigen gene A3 (MAGE-A3) is aberrantly expressed in a number of cancer types. Because of its high specificity, MAGE-A3 has shown to be a promising candidate for cancer immunotherapy. Dendritic cells (DCs) have emerged as the natural agents for antigen delivery. DCs transduced with antigen may increase immune response and maintain immune durability. The aim of this study was to investigate the roles of DCs transduced with lentiviral vectors (LVs) encoding full-length MAGE-A3 gene in cancer immunotherapy . METHODS: A LV containing full-length MAGE-A3 gene (rLV/MAGE-A3) was constructed. Reverse transcriptase-polymerase chain reaction and direct DNA sequencing were performed to verify the construct. Human DCs derived from umbilical cord blood were then transduced with rLV/MAGE-A3. The potency of rLV/MAGE-A3-transduced DCs was examined by measurement of surface markers and mixed lymphocyte reaction. The MAGE-A3-specific T-cell response induced by DCs was detected using the lactate dehydrogenase release assay. RESULTS: rLV/MAGE-A3 was constructed successfully and used to transduce DCs efficiently. DCs transduced with rLV/MAGE-A3 stably expressed MAGE-A3 and yielded high percentage of cells expressing CD80, CD86, and HLA-DR. rLV/MAGE-A3 transduction did not impair DCs viability and maturation at a multiplicity of infection of 30. The rLV/MAGE-A3-transduced DCs induced MAGE-A3-specific T lymphocytes that exhibited a significant lysis activity against MAGE-A3-bearing tumor cell lines (HuH-7 and SGC-7901). CONCLUSIONS: DC-directed rLV/MAGE-A3 efficiently induced antigen-specific immune responses, indicating the possibility of DC-based MAGE-A3 antigen vaccine as a promising strategy for treatment of MAGE-A3-associated cancer. FAU - Lin, Liyan AU - Lin L AD - Department of Pathology, Fujian Medical University, 88# Jiao Tong Road, Fuzhou, 350004, Fujian, People's Republic of China. FAU - Wei, Juanbing AU - Wei J FAU - Chen, Yuqing AU - Chen Y FAU - Huang, Aimin AU - Huang A FAU - Li, Kay Ka-Wai AU - Li KK FAU - Zhang, Wenmin AU - Zhang W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131210 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (MAGEA3 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Antigens, Neoplasm/genetics/*immunology/metabolism MH - Blotting, Western MH - Cancer Vaccines/*administration & dosage/immunology MH - Carcinoma, Hepatocellular/genetics/*immunology/therapy MH - Cell Proliferation MH - Cells, Cultured MH - Dendritic Cells/cytology/*immunology/metabolism MH - Flow Cytometry MH - Hepatocytes/*immunology/metabolism MH - Humans MH - Immunotherapy MH - Lentivirus/genetics MH - Liver Neoplasms/genetics/*immunology/therapy MH - Neoplasm Proteins/genetics/*immunology/metabolism MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stomach Neoplasms/genetics/*immunology/therapy MH - T-Lymphocytes/immunology/metabolism EDAT- 2013/12/11 06:00 MHDA- 2014/03/26 06:00 CRDT- 2013/12/11 06:00 PHST- 2013/06/12 00:00 [received] PHST- 2013/11/14 00:00 [accepted] PHST- 2013/12/11 06:00 [entrez] PHST- 2013/12/11 06:00 [pubmed] PHST- 2014/03/26 06:00 [medline] AID - 10.1007/s00432-013-1552-8 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2014 Feb;140(2):281-9. doi: 10.1007/s00432-013-1552-8. Epub 2013 Dec 10.