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CD44v10, osteopontin and lymphoma growth retardation by a CD44v10‐specific antibody
Author(s) -
Megaptche Amelie Pajip,
Erb Ulrike,
Büchler Markus Wolfgang,
Zöller Margot
Publication year - 2014
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2014.47
Subject(s) - osteopontin , antibody , cd44 , cancer research , biology , immunology , leukemia , inflammation , lymphoma , cell , genetics
Blockade of CD44 is considered a therapeutic option for the elimination of leukemia‐initiating cells. However, the application of anti‐panCD44 can be burdened by severe side effects. We determined whether these side effects could be avoided by replacing anti‐panCD44 with CD44 variant isoform (CD44v)‐specific antibodies in CD44v‐positive hematological malignancies using the EL4 thymoma and CD44v10‐transfected EL4 (EL4‐v10) as models. Subcutaneous growth of EL4 and EL4‐v10 was equally well inhibited by the anti‐panCD44 and anti‐CD44v10 antibodies, respectively. Ex vivo analysis indicated that natural killer cytotoxicity and antibody‐dependent cellular cytotoxicity were the main effector mechanisms. Under local inflammation, the efficacy of anti‐CD44v10 prolonged the survival time twofold compared with untreated, EL4‐v10 tumor‐bearing mice, and this was due to inflammation‐induced expression of osteopontin (OPN). A high level of OPN in EL4‐v10 tumors supported leukocyte recruitment and tumor‐infiltrating T‐cell activation. Taken together, in hematological malignancies expressing CD44v, anti‐panCD44 can be replaced by CD44v‐specific antibodies without a loss in efficacy. Furthermore, CD44v10‐specific antibodies appear particularly advantageous in cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte recruitment and activation.