In vitro immunization and expansion of antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy using peptide-pulsed dendritic cells.
The design of an effective procedure to sensitize and expand antigen-specific cytotoxic T lymphocytes (CTL) in vitro is essential for the development of effective adoptive cellular immunotherapy protocols for cancer. We have analyzed the capacity of tissue culture-derived dendritic cells (DC) to present specific peptide epitopes to CTL precursors. Our results demonstrate that peptide-pulsed DC were efficient in generating CTL responses specific for various viral and tumor epitopes. Furthermore, IL-7 and IL-10 potentiated the ability of the peptide-pulsed DC to trigger antigen-specific CTL responses. The CTL generated using this procedure efficiently recognized the naturally processed antigens and could be expanded approximately 100- to 1000-fold in tissue culture in 10 to 15 days without a loss of activity and specificity. The results and procedures described herein may facilitate the development of effective CTL-based adoptive immunotherapy for chronic viral diseases and cancer.
Tsai
V
V
Cytel Corporation, San Diego, CA 92121, USA.
Kawashima
I
I
Keogh
E
E
Daly
K
K
Sette
A
A
Celis
E
E
D019264:Adoptive Transfer / Q000379:methods*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D010455:Peptides