Phase I study of alpha-galactosylceramide-pulsed antigen presenting cells administration to the nasal submucosa in unresectable or recurrent head and neck cancer

Cancer Immunol Immunother. 2008 Mar;57(3):337-45. doi: 10.1007/s00262-007-0373-5. Epub 2007 Aug 10.

Abstract

Background: Human Valpha24 natural killer T (NKT) cells are activated by the specific ligand, alpha-galactosylceramide (alpha-GalCer), in a CD1d-dependent manner. Potent anti-tumor activity of activated NKT cells has been previously demonstrated.

Methods: We conducted a phase I study with alpha-GalCer-pulsed antigen presenting cells (APCs) administered in the nasal submucosa of patients with head and neck cancer, and evaluated the safety and feasibility of such a treatment. Nine patients with unresectable or recurrent head and neck cancer received two treatments 1 week apart, of 1 x 10(8) of alpha-GalCer-pulsed autologous APCs into the nasal submucosa.

Results: During the clinical study period, no serious adverse events (Common Terminology Criteria for Adverse Events version 3.0 greater than grade 3) were observed. After the first and the second administration of alpha-GalCer-pulsed APCs, an increased number of NKT cells was observed in four patients and enhanced natural killer activity was detected in the peripheral blood of eight patients.

Conclusion: The administration of alpha-GalCer-pulsed APCs into the nasal submucosa was found to be safe and induce anti-tumor activity in some patients.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / transplantation*
  • Cells, Cultured
  • Female
  • Galactosylceramides / pharmacology*
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Immunotherapy / methods*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Killer Cells, Natural / immunology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Transfusion / adverse effects
  • Lymphocyte Transfusion / methods*
  • Male
  • Middle Aged
  • Nasal Mucosa / immunology*
  • Phenotype
  • Recurrence
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Galactosylceramides
  • alpha-galactosylceramide
  • Interferon-gamma