3.4.21.78 additional information cell depleted bone marrow cells (TCD BM) and isolated T cell populations of wild type (WT) and gzmA-/- C57/BL6 donor mice are transferred into the BALB/c recipient mice after lethal irradiation. Immune tolerant and GvHD mice are monitored comparatively after adoptive T cell transfer for incidence, severity and clinical manifestation of GvHD by clinical and histopathological grading. After irradiation and transplantation the body weight of recipient mice declines in all treatment groups and increases again one week after transplantation. But two weeks after transplantation, mice from the GvHD group continuously lost weight in contrast to the immune tolerant groups. Histopathological investigations confirm a severe inflammation especially in the small and large intestine as GvHD target organs. Enzyme-deficient gzmA-/- Tregs cannot efficiently protect from GvHD-related inflammation and organ destruction in the intestinal tract with relevant crypt apoptosis detected in the small and large intestine 755083 3.4.21.78 additional information construction of a chimeric protein IGA, consisting of interleukin IL-2 and granzyme A, using IL-2 as a targeting moiety and granzyme A as a killing moiety to overcome multidrug resistance MDR in anticancer therapy. The IGA chimeric protein enters the target sensitive and MDR cancer cells overexpressing IL-2 receptor and induces caspase 3-independent cell death. After its entry, IGA causes a decrease in the mitochondrial potential, and triggers translocation of nm23-H1, a granzyme A-dependent DNase, from the cytoplasm to the nucleus, where it causes single-strand DNA nicks, thus causing cell death. IGA is able to overcome MDR and kill cells resistant to chemotherapeutic drugs 717675 3.4.21.78 additional information generation of GzmA-/- knockout mice, backcrossed into the C57BL/6 background more than 10 times -, 755118 3.4.21.78 additional information GzmA silencing by siRNA interference 753077 3.4.21.78 N153Q molecular replacement 653301 3.4.21.78 S176A mutated active site, does not cleave protein NDUFS3 697233