Human leukocyte antigen (HLA) matched allogeneic stem cell transplantation (SCT) is an established curative treatment for hematopoietic malignancies and an investigative immunotherapeutic approach... Show moreHuman leukocyte antigen (HLA) matched allogeneic stem cell transplantation (SCT) is an established curative treatment for hematopoietic malignancies and an investigative immunotherapeutic approach for solid tumors. The curative effect of allogeneic SCT is based on so called graft versus-tumor (GvT) responses. The GvT effect in the HLA-matched setting is mainly driven by donor immune responses against so called minor histocompatibility antigens (mHags). Emerging data suggest that immunotherapy targeting mHags may eradicate cancer without severe side effects. This thesis investigated 1) the proof of concept for the efficacy of mHag specific immunotherapy in vitro and in vivo, 2) the optimal circumstances under which mHag specific cytotoxic T-cells (CTLs) are most effective against established leukemia and solid tumors, 3) new immune escape mechanisms in cancer that need to be considered when targeting mHags, 4) the optimal protocols for the in vitro expansion of mHags CTLs, 5) the optimal design of mHag peptide vaccines and 6) the optimal parameters for the clinical guidance of mHags specific immunotherapy of cancer. The data acquired in this thesis have provided relevant knowledge that is already partially implemented in the design of new HA-1 vaccination studies aiming at curing leukemia and solid tumors. Show less
