The Journal of Experimental Medicine
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Published 2 May 2005. doi:10.1084/jem.20042592
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 9, 1503-1517
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ARTICLE

 Sustained expansion of NKT cells and antigen-specific T cells after injection of {alpha}-galactosyl-ceramide loaded mature dendritic cells in cancer patients

David H. Chang1, Keren Osman1, John Connolly2, Anjli Kukreja1, Joseph Krasovsky1, Maggi Pack2, Aisha Hutchinson1, Matthew Geller1, Nancy Liu1, Rebecca Annable1, Jennifer Shay4, Kelly Kirchhoff1, Nobusuke Nishi5, Yoshitaka Ando5, Kunihiko Hayashi5, Hani Hassoun3, Ralph M. Steinman2, and Madhav V. Dhodapkar1,3

1 Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University
2 Laboratory of Cellular Physiology and Immunology, The Rockefeller University
3 Memorial Sloan Kettering Cancer Center, New York, NY 10021
4 Baylor Institute of Immunology Research, Dallas, TX 75246
5 Pharmaceutical Division, Kirin Breweries Co. Ltd., 150-8011 Tokyo, Japan

CORRESPONDENCE Madhav V. Dhodapkar: dhodapm{at}rockefeller.edu

Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, {alpha}-galactosyl-ceramide ({alpha}-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of {alpha}-GalCer–pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-{gamma} inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to {alpha}-GalCer–loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo.

Abbreviations used: {alpha}-GalCer, {alpha}-galactosyl-ceramide; ANA, antinuclear antibody; Flu-MP, influenza matrix peptide; ICS, intracellular cytokine secretion; IP, IFN-{gamma}–inducible protein; MIP, macrophage inflammatory protein; RF, rheumatoid factor.


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