Our research is focusing on the major histocompatibility complex (MHC) molecules and the induction of antigen-specific adaptive as well as innate immune responses. This includes structural characterization of MHC genes through direct sequencing, functional studies to determine peptide binding motifs from recombinant MHC molecules, as well as the identification and expansion of HLA/ligand-specific T cells. In particular the work focuses on the identification of anti-tumor as well as antiviral T-cell epitopes and the characterization and expansion of ligand-specific T cells. The work also includes the influence of heat shock protein (HSP) 70-mediated cross-presentation of target antigens, the role of suppressors of cytokine signalling (SOCS) in T-cell function and the signalling pathways involved (Figure 1).
Furthermore we are developing personalized antiviral as well as anti-tumor T-cell immunotherapeutics and established the allogeneic cell registry alloCELL (www.allocell.org), which provides a source of third party T-cell donors. Manufacturing license according to the German Medicines Act (AMG) for isolation of clinical-grade antiviral T cells for the adoptive T-cell transfer by using the interferon-gamma (IFN-γ) Cytokine Capture Systems (CCS) and overlapping viral peptide pools was obtained.
A three-step protocol for the rapid generation of clinical-grade antiviral T cells was established to facilitate the manufacture of specific T cells for adoptive transfer in pre-monitored patients. First Step: Selection of potential T-cell donors from the alloCELL registry (HLA type, virus serology and virus-specific T-cell response). Second Step: Verification of the donor’s specific T-cell frequencies and prediction of the donor’s T-cell enrichment efficiency by small-scale MiniMACS CSA. Third Step: Manufacturing of clinical-grade antiviral T cells by large-scale CliniMACS CCS.
Further research interest
1. adoptive T-cell transfer
2. HLA in stem cell transplantation
3. role of Damps in the immune response