Cytotoxic T cells reactive to an immunodominant leukemia-associated antigen can be specifically primed and expanded by combining a specific priming step with nonspecific large-scale expansion

Arnab Ghosh, Matthias Wolenski, Christoph Klein, Karl Welte, Bruce R. Blazar, Martin G. Sauer

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Identification of dominant leukemia-associated neoantigens and favoring specific priming and subsequent expansion of T cells reactive to these antigens might harbor therapeutic potential. Here, a new strategy combines a specific T-cell activation step using tumor lysate-pulsed bone marrowderived dendritic cells with a nonspecific large-scale expansion method. The leukemia cell line C1498 transduced with a potentially immunodominant antigen (ovalbumin) was used to track expansion and functionality of antigen-specific cytotoxic T cell (CTL), both in vitro and in vivo. Three times more leukemia-specific CTL could be generated when compared with the respective controls. CTL generated after increasing the antigen-specific T-cell precursor frequency in vitro cured up to 80% of mice bearing leukemia with the respective antigen (P>0.005, as compared with controls). Alternatively, the yield of CTL reactive to a immunodominant neoantigen increased by factor 2 to 6 when T-cell donors were immunized with dendritic cell presenting the respective antigen. However, increasing the leukemia-reactive precursor frequency to a clinically exploitable level will be the key for the design of successful T-cell therapy trials.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalJournal of Immunotherapy
Volume31
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • Adoptive immunotherapy
  • CTL
  • Dendritic cells
  • Expander beads
  • Immunization
  • Leukemia
  • Mouse

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