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Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

The authors thank Mrs. Meiqin Gao for her excellent technical assistance. This research was supported by the grant of Natural Science Foundation of Fujian Province (C0610023, 2012J01362) and Fujian Medical University Fund (09ZD007).

Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene”.

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Authors and Affiliations

  1. Department of Pathology, Fujian Medical University, 88# Jiao Tong Road, Fuzhou, 350004, Fujian, People’s Republic of China

    Liyan Lin, Yuqing Chen, Aimin Huang & Wenmin Zhang

  2. Fujian Provincial Cancer Hospital, Teaching Hospital, Fujian Medical University, Fuzhou, 350014, Fujian, People’s Republic of China

    Liyan Lin

  3. Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350004, Fujian, People’s Republic of China

    Juanbing Wei

  4. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China

    Kay Ka-Wai Li

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  1. Liyan Lin
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  2. Juanbing Wei
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  3. Yuqing Chen
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  4. Aimin Huang
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  5. Kay Ka-Wai Li
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  6. Wenmin Zhang
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Correspondence to Wenmin Zhang.

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Liyan Lin and Juanbing Wei have contributed equally to this work and should be considered co-first authors.

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Lin, L., Wei, J., Chen, Y. et al. Induction of antigen-specific immune responses by dendritic cells transduced with a recombinant lentiviral vector encoding MAGE-A3 gene. J Cancer Res Clin Oncol 140, 281–289 (2014). https://doi.org/10.1007/s00432-013-1552-8

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  • DOI: https://doi.org/10.1007/s00432-013-1552-8

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