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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2002-11-3580.
Submitted December 9, 2002
Accepted June 25, 2003
Testing of recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24
Maurizio Chiriva-Internati, Yong Liu, Jon A Weidanz, Fabio Grizzi, Hong You, Weiping Zhou, Klaus Bumm, Bart Barlogie, Jawahar L Mehta, and Paul L Hermonat*
Department of Internal Medicine, University of Arkansa for Medical Sciences, Little Rock, AR, USA; Gene Therapy Center in Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Department of Internal Medicine, Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, USA
Scientific Direction, Instituto Clinico Humanitas, Milan, Italy; Institute for Viral Hepatitis, Chonqing Medical University, Chongqing, China
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, USA; Institute for Viral Hepatitis, Chonqing Medical University, Chongqing, China
* Corresponding author; email: hermonatpaull{at}uams.edu.
Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen-loading of dendritic cells generates significant and rapid (one stimulation/one week) cytotoxic T lymphocyte (CTL) responses in vitro against viral antigens. As a more extensive analysis of the rAAV system we have used a self-antigen, HM1.24, expressed in multiple myeloma (MM). Again, with one stimulation, significant MHC Class I-restricted, anti-HM1.24-specific CTL killing was demonstrated against multiple MM cells. Furthermore, higher expression of interferon-gamma in T cells and higher expression levels of, in order of significance, CD80 (2.6-3.8 fold increase), CD86, and CD40 on DC were also observed. The use of synthetic HM1.24-positive target cells further demonstrated the antigen-specificity of these CTL. There was also no evidence of natural killer cell involvement. These data extend our earlier studies, and suggest that the rAAV-loading of DC may be a particularly good protocol for generating CTL against self-antigens which may not otherwise be considered good targets due to their low immunogenicity. We also show that HM1.24 may be an effective antigen for targeting MM.
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