PMID- 11127395 OWN - NLM STAT- MEDLINE DCOM- 20010222 LR - 20191025 IS - 0888-0018 (Print) IS - 0888-0018 (Linking) VI - 17 IP - 8 DP - 2000 Dec TI - Childhood all blasts retain phenotypic and genotypic characteristics upon long-term serial passage in NOD/SCID mice. PG - 635-50 AB - For children with an early bone marrow relapse or relapsed T-cell acute lymphoblastic leukemia (ALL), allogeneic bone marrow transplantation (BMT) is currently the only therapeutic option with a curative approach. Here, the graft versus leukemia (GvL) effect seems to play an important role for long-term immunological control of leukemia. If a bone marrow donor is not available, autologous stem cell transplantation after high-dose chemotherapy has been used as an alternative option. The objective of this work was the induction of tumor specific cytotoxic T-lymphocytes (CTL) against autologous leukemic cells in order to generate the missing GvL effect after autoBMT. The first step was the establishment of an optimized and reliable mouse model. The second step was the induction of a GvL effect in an allogeneic approach to serve as a basis for further GvL experiments in an autologous approach in this mouse model. Leukemic cells from 11 out of 16 different pediatric patients were successfully established in mice and in one case passaged over 19 generations without changes of genotype or phenotype. The antileukemic activity of allogeneic human MNC as a GvL reaction and an accompanying GvHD in the mouse model was shown. Xenotransplanted ALL can be considered a clinically relevant model mimicking the human conditions and as a useful preclinical tool for the evaluation of novel immuno- or genetherapeutic approaches. FAU - Borgmann, A AU - Borgmann A AD - Department of Pediatric Oncology/Hematology, Charite, Campus Virchow-Klinikum, Berlin, Germany. FAU - Baldy, C AU - Baldy C FAU - von Stackelberg, A AU - von Stackelberg A FAU - Beyermann, B AU - Beyermann B FAU - Fichtner, I AU - Fichtner I FAU - Nurnberg, P AU - Nurnberg P FAU - Henze, G AU - Henze G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Pediatr Hematol Oncol JT - Pediatric hematology and oncology JID - 8700164 RN - 0 (Interleukin-2) SB - IM MH - Adolescent MH - Animals MH - Cell Division MH - Child MH - Child, Preschool MH - DNA Fingerprinting MH - Female MH - Genotype MH - Graft vs Host Disease/immunology/pathology MH - Humans MH - Immunophenotyping MH - Interleukin-2/pharmacology MH - Leukocytes, Mononuclear/drug effects/immunology MH - Male MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Neoplasm Transplantation/*methods MH - Phenotype MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/*immunology/pathology MH - T-Lymphocytes, Cytotoxic/drug effects/immunology MH - Transplantation, Heterologous EDAT- 2000/12/29 11:00 MHDA- 2001/03/03 10:01 CRDT- 2000/12/29 11:00 PHST- 2000/12/29 11:00 [pubmed] PHST- 2001/03/03 10:01 [medline] PHST- 2000/12/29 11:00 [entrez] AID - 10.1080/08880010050211349 [doi] PST - ppublish SO - Pediatr Hematol Oncol. 2000 Dec;17(8):635-50. doi: 10.1080/08880010050211349.