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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v18.i1-2.80
pages 65-75

In Vitro Immunization and Expansion of Antigen-Specific Cytotoxic T Lymphocytes for Adoptive Immunotherapy Using Peptide-Pulsed Dendritic Cells

Van Tsai
Cytel Corporation, San Diego, CA
Ichiro Kawashima
Takara Shuzo Co., Ltd, Biotechnology Research Laboratories, Otsu, Shiga, Japan
Elissa Keogh
Cytel Corporation, San Diego, CA
Kieran Daly
Cytel Corporation, San Diego, CA
Alessandro Sette
Cytel Corporation, San Diego, CA
Esteban Celis
Cytel Corporation, San Diego, CA

ABSTRACT

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.