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01-12-2011 | Original Article

Targeting of a developmentally regulated epitope of CD43 for the treatment of acute leukemia

Authors: Yoon Kyung Jeon, Hye Sook Min, Yoo Jeong Lee, Byung Hyun Kang, Eun Ji Kim, Hyo Jin Park, Youngmee Bae, Hyun Gyu Lee, Weon Seo Park, Hyung Geun Song, Kyeong Cheon Jung, Seong Hoe Park

Published in: Cancer Immunology, Immunotherapy | Issue 12/2011

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.

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Title: Targeting of a developmentally regulated epitope of CD43 for the treatment of acute leukemia
Authors: Yoon Kyung Jeon
Hye Sook Min
Yoo Jeong Lee
Byung Hyun Kang
Eun Ji Kim
Hyo Jin Park
Youngmee Bae
Hyun Gyu Lee
Weon Seo Park
Hyung Geun Song
Kyeong Cheon Jung
Seong Hoe Park
Publication date: 01-12-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 12/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1066-7

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