title: Targeting of a developmentally regulated epitope of CD43 for the treatment of acute leukemia.
abstract: Previously, we developed a JL1 mouse monoclonal antibody that specifically recognizes the leukemic cells of T, B, and myeloid lineages, but not the peripheral blood cells and pluripotent hematopoietic stem cells. Here, we identified that JL1 mAb recognized a specific epitope of human CD43 and validated its potential as an anti-leukemic targeting agent. After the comprehensive screening of JL1 Ag in the human thymocyte cDNA library, multiple fusion gene constructs encoding human CD43 were generated to identify its specific epitope to JL1 antibody. JL1 antibody interacted with a developmentally regulated and non-glycosylated epitope of the human CD43 extracellular domain (AA 73-81, EGSPLWTSI). In an in vivo leukemia model using NOD/SCID mice injected with CCRF-CEM7 cells, JL1 antibody induced effective cytotoxicity in tumor cells and prolonged survival (p < 0.05). Saporin conjugation to JL1 antibody effectively depleted tumor cells in in vitro cytotoxic assays and also prolonged survival in a leukemic mouse model (p < 0.001). These preclinical results further support the therapeutic potential of the JL1 antibody in the management of acute leukemia.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.forename: Yoo Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Byung Hyun
authors.initials: BH
authors.lastname: Kang
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Bae
authors.forename: Hyun Gyu
authors.initials: HG
authors.lastname: Lee
authors.forename: Weon Seo
authors.initials: WS
authors.lastname: Park
authors.forename: Hyung Geun
authors.initials: HG
authors.lastname: Song
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
authors.forename: Seong Hoe
authors.initials: SH
authors.lastname: Park
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015153:Blotting, Western; D002469:Cell Separation; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D015456:Leukemia, Biphenotypic, Acute / Q000188:drug therapy* / Q000276:immunology; D051917:Leukosialin / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D051917:Leukosialin