Double loading of dendritic cell MHC class I and MHC class II with an AML antigen repertoire enhances correlates of T-cell immunity in vitro via amplification of T-cell help

William K. Decker, Dongxia Xing, Sufang Li, Simon N. Robinson, Hong Yang, Xin Yao, Harry Segall, John D. McMannis, Krishna V. Komanduri, Richard E. Champlin, Elizabeth J. Shpall

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Therapeutic vaccination with dendritic cells presenting tumor-specific antigens is now recognized as an important investigational therapy for the treatment of neoplastic disease. Dendritic cell cross-presentation is credited with the ability of tumor lysate-loaded dendritic cells to prime both CD4 and CD8-specific T-lymphocyte responses, enabling the generation of cancer specific CTL activity without the loading of the classical MHC class I compartment. Recently, however, several reports have raised doubts as to the efficiency of cross-presentation as a mechanism for CTL priming in vivo. To examine this issue, we have doubly-loaded human dendritic cells with both AML-specific tumor lysate and AML-specific tumor mRNA. Our results show that these doubly-loaded dendritic cells can mediate superior primary, recall, and effector lytic responses in vitro in comparison to those of dendritic cells loaded with either tumor lysate or tumor mRNA alone. Enhanced recall responses appeared to be influenced by CD40/CD40L signaling, underscoring the importance of T-cell help in the generation and perpetuation of the adaptive immune response.

Original languageEnglish (US)
Pages (from-to)3203-3216
Number of pages14
JournalVaccine
Volume24
Issue number16
DOIs
StatePublished - Apr 12 2006
Externally publishedYes

Keywords

  • AML
  • Dendritic Cells
  • T-cell Help
  • Vaccination

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

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  • Cite this

    Decker, W. K., Xing, D., Li, S., Robinson, S. N., Yang, H., Yao, X., Segall, H., McMannis, J. D., Komanduri, K. V., Champlin, R. E., & Shpall, E. J. (2006). Double loading of dendritic cell MHC class I and MHC class II with an AML antigen repertoire enhances correlates of T-cell immunity in vitro via amplification of T-cell help. Vaccine, 24(16), 3203-3216. https://doi.org/10.1016/j.vaccine.2006.01.029