CD52 antigen expressed by malignant plasma cells can be targeted by alemtuzumab in vivo in NOD/SCID mice.
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.
Carlo-Stella
Carmelo
C
Cristina Gandini Medical Oncology Unit, Istituto Nazionale Tumori, Milano, Italy. carmelo.carlostella@unimi.it
Guidetti
Anna
A
Di Nicola
Massimo
M
Longoni
Paolo
P
Cleris
Loredana
L
Lavazza
Cristiana
C
Milanesi
Marco
M
Milani
Raffaella
R
Carrabba
Matteo
M
Farina
Lucia
L
Formelli
Franca
F
Gianni
Alessandro M
AM
Corradini
Paolo
P
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
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