title: CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific antibody.
abstract: 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.
authors.affiliation: Department of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.
authors.forename: Amelie Pajip
authors.initials: AP
authors.lastname: Megaptche
authors.affiliation: Department of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erb
authors.affiliation: Allgemeine, Viszeral- und Transplantationschirurgie, University Hospital of Surgery, Heidelberg, Germany.
authors.forename: Markus Wolfgang
authors.initials: MW
authors.lastname: Büchler
authors.affiliation: Department of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.
authors.forename: Margot
authors.initials: M
authors.lastname: Zöller
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117722:CD44v10 antigen; D018960:Hyaluronan Receptors; D053495:Osteopontin