Abstract vom Kongress in Wien (S. 451)
Usage of memory T cell subpopulations for adoptive T cell therapy
A. Djordjevic
, B. Mosetter, B. Frankenberger;
Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany.
Introduction: According to the latest state of research central memory T cells (Tcm) have demonstrated promising efficacy for adoptive T cell therapy (ATT) in a mouse infection
model.
Materials and Methods: We focus on the isolation of highly purified Tcm and stem cell like memory T cells (Tscm) by enrichment via magnetic beads and cell sorting. We have already
established a multiplicity of T cell receptors (TCRs) specific for different tumor-associated antigens (TAAs) with high functional avidity. Following transfer of clinically promising TCRs
into Tcm and/or Tscm efficacy will be analyzed in pre-clinical in vivo NSG (NOD/SCID IL-2Rγnull) tumor mouse models.
Results: Using magnetic beads enrichment kits we gained purity of viable memory T cell subpopulations of over 90%. Furthermore, usage of specific cytokine cocktails have been
proven to modulate the differentiation status of ex vivo-cultured
T cells. Accordingly, following cultivation of CD3+ cells in an 11-days experiment adding IL-2 to the culture medium
for 4 days followed by incubation with IL-21 and IL-12 for 3 days and finally with solely IL-21 for additional 4 days, we could demonstrate an increase of Tcm from 20% to 65%.
Conclusions: Adoptive transfer of TCR-transgenic T cells towards clinical evaluation needs careful pre-clinical assessment of multiple parameters. Here we focus on the definition of
the ‘ideal’ recipient T cell subpopulation for transduction with selected TCRs specific for TAAs and in vivo efficacy in a NSG tumor mouse model.
This work was supported by the German Research Foundation (SFB-TR36)
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