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Clinical Trials with α-Galactosylceramide (KRN7000) in Advanced Cancer

  • Famke L. Schneiders
  • Rik J. Scheper
  • Hetty J. Bontkes
  • B. Mary E. von Blomberg
  • Alfons J. M. van den Eertwegh
  • Tanja D. de Gruijl
  • Hans J. van der VlietEmail author
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

For over a century, research has sought ways to boost the immune system of cancer patients in order to eradicate tumors that arose after escaping presumptive immunosurveillance. With increasing knowledge of the immune system, immunotherapeutic strategies to break tolerance to the tumor evolved from largely nonspecific to more specific and increasingly potent forms of cancer vaccination. Overall however, immunotherapeutic strategies for the treatment of cancer have had limited clinical success and an urgent need exists, therefore, to introduce more effective, knowledge-based therapeutic approaches. Invariant natural killer T (iNKT) cells constitute an evolutionary conserved T lymphocyte lineage with dominant immunoregulatory and antitumor effector cell properties. iNKT specifically recognize the glycolipid α-galactosylceramide (α-GalCer/KRN7000) in the context of the CD1d antigen-presenting molecule resulting in their activation. Activated iNKT have been shown to promote the development of a long-lasting Th1-biased proinflammatory antitumor immune response in a variety of murine tumor-metastasis models of liver, lung and lymph nodes, including colon and lung carcinoma, lymphoma, sarcoma, and melanoma, suggesting broad clinical applicability. Here, we will provide an overview of the preclinical data of α-GalCer that formed the basis for subsequent clinical trials in advanced cancer patients, review these clinical trials, focusing on our own experience with α-GalCer, and discuss future perspectives.

Keywords

iNKT Cell National Cancer Institute Common Toxicity Criterion iNKT Cell Activation Mature moDC Antitumor Effector Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Our work is supported by grant no. 90700309 from The Netherlands Organization for Health Research and Development (ZonMw) and grant VU2010-4728 from the Dutch Cancer Society (KWF)

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Famke L. Schneiders
    • 1
  • Rik J. Scheper
    • 1
  • Hetty J. Bontkes
    • 1
  • B. Mary E. von Blomberg
    • 1
  • Alfons J. M. van den Eertwegh
    • 1
  • Tanja D. de Gruijl
    • 1
  • Hans J. van der Vliet
    • 2
    Email author
  1. 1.Department of Medical OncologyVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Medical OncologyVU University Medical CenterAmsterdamThe Netherlands

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