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-s pecific cytotoxic T lymphocytes (CTL) in vitro is essential for the de velopment of effective adoptive cellular immunotherapy protocols for c ancer. We have analyzed the capacity of tissue culture-derived dendrit ic cells (DC) to present specific peptide epitopes to CTL precursors. Our results demonstrate that peptide-pulsed DC were efficient in gener ating CTL responses specific for various viral and tumor epitopes, Fur thermore, 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 antigen s and could be expanded approximately 100- to 1000-fold in tissue cult ure in 10 to 15 days without a loss of activity and specificity. The r esults and procedures described herein may facilitate the development of effective CTL-based adoptive immunotherapy for chronic viral diseas es and cancer.