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CD1d-Restricted T Cells License B Cells to Generate Long-Lasting Cytotoxic Antitumor Immunity In vivo

Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Kwanakgu, Seoul, Korea

Requests for reprints: Chang-Yuil Kang, Laboratory of Immunology, College of Pharmacy, Seoul National University, Shillim-9-dong, Kwanakgu, Seoul 151-742, Korea. Phone: 82-2-880-7860; Fax: 82-2-885-1373; E-mail: cykang{at}snu.ac.kr.

Although resting B cells are known for being poorly immunogenic and for inducing T-cell tolerance, we have here attempted to test whether their immunogenicity could be enhanced by CD1d-restricted invariant T cells (iNKT) to a point where they could be used in cellular vaccines. We found that the addition of the iNKT ligand -galactosylceramide (GalCer) to peptide-loaded B cells overcame peptide-specific T-cell unresponsiveness and allowed for the generation of peptide-specific memory CTL immunity. This CTL was induced independently of CD4 T and natural killer cells but required iNKT and CD8 T cells. B cells directly primed CTL, and the GalCer and the peptide must be presented on the same cell. Importantly, our B-cell–based vaccine is comparable in efficiency with dendritic cell–based vaccines, inducing similar CTL responses as well as providing an effective regimen for preventing and suppressing s.c. and metastatic tumors. Therefore, with the help of iNKT, peptide-pulsed B cells can establish long-lasting antitumor immunity and so show promise as the basis for an alternative cell-based vaccine. (Cancer Res 2006; 66(13): 6843-50)

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