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

• David H. Chang

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Keren Osman

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• John Connolly

  2Laboratory of Cellular Physiology and Immunology, The Rockefeller University

• Anjli Kukreja

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Joseph Krasovsky

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Maggi Pack

  2Laboratory of Cellular Physiology and Immunology, The Rockefeller University

• Aisha Hutchinson

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Matthew Geller

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Nancy Liu

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Rebecca Annable

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Jennifer Shay

  4Baylor Institute of Immunology Research, Dallas, TX 75246

• Kelly Kirchhoff

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

• Nobusuke Nishi

  5Pharmaceutical Division, Kirin Breweries Co. Ltd., 150-8011 Tokyo, Japan

• Yoshitaka Ando

  5Pharmaceutical Division, Kirin Breweries Co. Ltd., 150-8011 Tokyo, Japan

• Kunihiko Hayashi

  5Pharmaceutical Division, Kirin Breweries Co. Ltd., 150-8011 Tokyo, Japan

• Hani Hassoun

  3Memorial Sloan Kettering Cancer Center, New York, NY 10021

• Ralph M. Steinman

  2Laboratory of Cellular Physiology and Immunology, The Rockefeller University

• Madhav V. Dhodapkar

  1Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University

抄録

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, α-galactosyl-ceramide (α-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of α-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-γ inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to α-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.

収録刊行物

• The Journal of Experimental Medicine

  The Journal of Experimental Medicine 201 (9), 1503-1517, 2005-05-02

  Rockefeller University Press

キーワード

• Immunology
• Immunology and Allergy

詳細情報

• CRID: 1361137043445305088
• NII論文ID: 30017434752
• DOI: 10.1084/jem.20042592
• ISSN: 15409538
• ISSN: 00221007
• Web Site: https://rupress.org/jem/article-pdf/201/9/1503/1718039/jem20191503.pdf
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