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Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells

Cancer Gene Therapy volume 12, pages 304–312 (2005)Cite this article

Abstract

Antigen-targeted immunotherapy is an emerging treatment for breast cancer. However, useful breast cancer antigens are only found in a subset of cancer patients. BA46, also known as lactadherin, is a membrane-associated glycoprotein that is expressed in most breast cancer cells but not in general hematopoietic cell populations. Moreover, it is much more difficult to generate CTLs against self-antigens. We wished to determine if the use of recombinant adeno-associated virus (rAAV) type 2 vectors for gene-loading of dendritic cells (DCs) could generate rapid, effective cytotoxic T lymphocytes (CTLs) against BA46. We were able to demonstrate that AAV/BA46/Neo-loading of DCs resulted in: (1) BA46 expression in DCs, (2) chromosomal integration of the AAV/BA46/Neo vector within DCs, (3) strong, rapid BA46-specific, MHC class I-restricted CTLs in only 1 week, (4) T-cell populations with significant interferon-γ (IFN-γ) expression but low IL-4 expression, (5) high CD80 and CD86 expression in DCs, and (6) high CD8:CD4 and CD8:CD56 T cell ratios. These data suggest that rAAV-loading of DCs may be useful for immunotherapeutic protocols against self-antigens in addition to viral antigens and that the BA46 antigen is potentially appropriate for cell-mediated immunotherapeutic protocols addressing ductal breast cancer.

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Acknowledgements

Drs Yong Liu and Maurizio Chiriva-Internati contributed equally to this work. This work was funded by a grant from the Arkansas Foundation for Breast Cancer Research.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, Arkansas, 72205, USA

    Yong Liu & Paul L Hermonat

  2. Department of Microbiology and Immunology, Texas Tech University, Lubbock, Texas, 79430, USA

    Maurizio Chiriva-Internati & Everardo Cobos

  3. Department of Oncology, Nanfang Hospital, Guangzhou, Guangdong, China

    Changxuan You & Rongcheng Luo

  4. Department of Obstetrics and Gynecology, Slot 518, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, Arkansas, 72205, USA

    Hong You, C Krishna Prasad, V Suzanne Klimberg, Helen Kay, Jawahar L Mehta & Paul L Hermonat

  5. Scientific Direction, Instituto Clinico Humanitas, Rozzano, Milano, Italy

    Fabio Grizzi

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  1. Yong Liu
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Correspondence to Paul L Hermonat.

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Liu, Y., Chiriva-Internati, M., You, C. et al. Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells. Cancer Gene Ther 12, 304–312 (2005). https://doi.org/10.1038/sj.cgt.7700785

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