title: CD52 antigen expressed by malignant plasma cells can be targeted by alemtuzumab in vivo in NOD/SCID mice.
abstract: OBJECTIVE
  To explore new treatments specifically targeting malignant plasma cells (PCs), we examined CD52 antigen expression on primary PCs as well as multiple myeloma (MM) cell lines, and investigated in vivo the antimyeloma activity of alemtuzumab.
  
  
  METHODS
  PCs were enriched from the marrow of MM patients (n = 39) according to CD138 expression and then analyzed by 3-color flow cytometry and quantitative PCR. The in vivo activity of alemtuzumab was evaluated in a xenotransplant model of MM in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.
  
  
  RESULTS
  CD52 expression revealed a substantial heterogeneity in terms of both percentage of positive cells and fluorescence intensity, with 25/39 (64%) MM patients showing >or=30% CD138(+) PCs expressing the CD52 antigen (mean = 79%; range, 33-100%). Similarly to primary cells, cell lines showed heterogeneous CD52 expression. Expression of CD52 mRNA by quantitative PCR analysis strongly correlated with CD52 antigen detection by flow cytometry. In vivo, alemtuzumab treatment significantly increased the median survival of animals with an early- (64 vs 77 days, p <or= 0.0005) or advanced-stage (66 vs 75 days, p <or= 0.02) disease.
  
  
  CONCLUSIONS
  We conclude that: 1) CD52 is expressed on PCs of a significant proportion of MM patients; 2) alemtuzumab used as a single agent exerts a good antitumor activity in NOD/SCID mice bearing an early-stage disease; and 3) alemtuzumab might have therapeutic potential in a subset of MM patients.
authors.affiliation: Cristina Gandini Medical Oncology Unit, Istituto Nazionale Tumori, Milano, Italy. carmelo.carlostella@unimi.it
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: Anna
authors.initials: A
authors.lastname: Guidetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Paolo
authors.initials: P
authors.lastname: Longoni
authors.forename: Loredana
authors.initials: L
authors.lastname: Cleris
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lavazza
authors.forename: Marco
authors.initials: M
authors.lastname: Milanesi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Milani
authors.forename: Matteo
authors.initials: M
authors.lastname: Carrabba
authors.forename: Lucia
authors.initials: L
authors.lastname: Farina
authors.forename: Franca
authors.initials: F
authors.lastname: Formelli
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D015703:Antigens, CD / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000074301:CD52 Antigen; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D053668:Syndecan-1; D053667:Syndecans; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012334:RNA, Neoplasm; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D000074323:Alemtuzumab