Testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24.
Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates significant and rapid (one stimulation per 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 major histocompatibility complex (MHC) class 1-restricted, anti-HM1.24-specific CTL killing was demonstrated against MM cells. Furthermore, higher expression of interferon-gamma (IFN-gamma) in T cells and higher expression levels of, in order of significance, CD80 (2.6- to 3.8-fold increase), CD86, and CD40 on DCs were also observed. The use of synthetic HM1.24-positive target cells further demonstrated the antigen specificity of these CTLs. There was also no evidence of natural killer cell involvement. These data extend our earlier studies and suggest that the rAAV-loading of DCs may be a particularly good protocol for generating CTLs against self-antigens, which may not otherwise be considered good targets because of their low immunogenicity. We also show that HM1.24 may be an effective antigen for targeting MM.
Chiriva-Internati
Maurizio
M
Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR 72205, USA.
Liu
Yong
Y
Weidanz
Jon A
JA
Grizzi
Fabio
F
You
Hong
H
Zhou
Weiping
W
Bumm
Klaus
K
Barlogie
Barthel
B
Mehta
Jawahar L
JL
Hermonat
Paul L
PL
D000951:Antigens, Neoplasm / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014161:Transduction, Genetic / Q000592:standards*
D000951:Antigens, Neoplasm; D001324:Autoantigens; D007371:Interferon-gamma