title: Antibody targeting of CD24 efficiently retards growth and influences cytokine milieu in experimental carcinomas.
abstract: BACKGROUND
  The targeting of cancer stem cells by monoclonal antibodies offers new options for therapy. CD24 is a glycosylphosphatidylinositol-anchored membrane protein with a small protein core and a high level of glycosylation. It is overexpressed in many human carcinomas and is correlated with poor prognosis. CD24 is a marker for pancreatic and ovarian cancer stem cells, whereas breast cancer stem cells are negative for CD24. In cancer cell lines, changes of CD24 expression can alter cellular properties in vitro and tumour growth in vivo. We have shown before that monotherapy with monoclonal antibody (mAb) SWA11 to CD24 effectively retarded tumour growth in xenotransplanted mice.
  
  
  METHODS
  Here, we have investigated in more detail the molecular mechanisms of mAb SWA11 therapeutic effects in A549 lung and SKOV3ip ovarian carcinoma models in scid/beige and CD1 mice, respectively. We focused on anti-proliferative, pro-apoptotic, anti-angiogenic and microenvironmental effects of SWA11 mAb treatment.
  
  
  RESULTS
  We find that CD24 targeting is associated with changes in tumour cell proliferation and angiogenesis. The treatment lead to increased infiltration of tumour tissues with immune cells suggesting involvement of ADCC. We found that SWA11 mAb treatment strongly altered the intratumoural cytokine microenvironment. The addition of SWA11 mAb to gemcitabine treatment strongly potentiated its anti-cancer efficacy in A549 lung cancer model.
  
  
  CONCLUSIONS
  Our data demonstrate that targeting of CD24 could be beneficial for the anti-cancer treatment combined with standard chemotherapy regimes.
authors.affiliation: Department of Translational Immunology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: A V
authors.initials: AV
authors.lastname: Salnikov
authors.forename: N P
authors.initials: NP
authors.lastname: Bretz
authors.forename: C
authors.initials: C
authors.lastname: Perne
authors.forename: J
authors.initials: J
authors.lastname: Hazin
authors.forename: S
authors.initials: S
authors.lastname: Keller
authors.forename: M
authors.initials: M
authors.lastname: Fogel
authors.forename: I
authors.initials: I
authors.lastname: Herr
authors.forename: T
authors.initials: T
authors.lastname: Schlange
authors.forename: G
authors.initials: G
authors.lastname: Moldenhauer
authors.forename: P
authors.initials: P
authors.lastname: Altevogt
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D051927:CD24 Antigen / Q000276:immunology* / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D051927:CD24 Antigen; D016207:Cytokines; D003841:Deoxycytidine; D000093542:Gemcitabine