Cancer Immunology, Immunotherapy

, Volume 55, Issue 9, pp 1122–1131

NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity

Authors

  • Takuya Osada
    • Duke University Medical Center
  • Timothy Clay
    • Duke University Medical Center
  • Amy Hobeika
    • Duke University Medical Center
  • H. Kim Lyerly
    • Duke University Medical Center
    • Duke University Medical Center
Original Article

DOI: 10.1007/s00262-005-0089-3

Cite this article as:
Osada, T., Clay, T., Hobeika, A. et al. Cancer Immunol Immunother (2006) 55: 1122. doi:10.1007/s00262-005-0089-3

Abstract

Recent reports revealed that dendritic cell (DC)–natural killer (NK) cell interaction plays an important role in tumor immunity, but few DC vaccine studies have attempted to evaluate the non-specific, yet potentially clinically relevant, NK response to immunization. In this study, we first analyzed in vitro activation of NK cells by DCs similar to those used in clinical trials. Subsequently, NK cell responses were analyzed in a phase I clinical trial of a vaccine consisting of autologous DCs loaded with a fowlpox vector encoding CEA. The data were compared with the clinical outcome of the patients. DC enhances NK activity in vitro, partly by sustaining NK cell survival and by enhancing the expression of NK-activating receptors, including NKp46 and NKG2D. Among nine patients in our clinical trial, NK cytolytic activity increased in four (range 2.5–5 times greater lytic activity) including three who had increased NK cell frequency, was stable in two and decreased in three. NKp46 and NKG2D expression showed a good correlation with the patients’ NK activity. When patients were grouped by clinical activity (stable disease/no evidence of disease (stable/NE, n=5) vs progressive disease (N=4) at 3 months), the majority in the stable/NE group had increases in NK activity (P=0.016). Anti-CEA T cell response was enhanced in all the nine patients analyzed, but was not significantly different between the two groups (P=0.14). Thus, NK responses following DC vaccination may correlate more closely with clinical outcome than do T cell responses. Monitoring of NK response during vaccine studies should be routinely performed.

Keywords

Natural killer cellDendritic cellVaccineClinical trial

Copyright information

© Springer-Verlag 2005