Targeting CD99 in association with doxorubicin: an effective combined treatment for Ewing's sarcoma.
CD99 is a 32kDa surface glycoprotein that is involved in the migration of leukocytes, cell-cell adhesion and apoptosis of T cells and Ewing's sarcoma (ES) cells, two cell types with a high level of CD99 expression. Engagement of the molecule induces a rapid death signal that appears to be related to the level of expression of this antigen. The rapid apoptosis induced by agonistic anti-CD99 monoclonal antibodies is of clinical interest in ES, a tumour for which no new drugs have been described as clearly effective in the last 10 years. In this study, we show that an anti-CD99 monoclonal antibody can be used to advantage in association with doxorubicin. Striking effectiveness was observed against local tumours and metastases. No remarkably toxic effects of anti-CD99 monoclonal antibody were found in bone marrow against blood precursors. These results provide the necessary rationale and support for a novel modality of therapeutic intervention, which may have application in the care of patients with ES.
Scotlandi
Katia
K
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna 40136, Italy. katia.scotlandi@ior.it
Perdichizzi
Stefania
S
Bernard
Ghislaine
G
Nicoletti
Giordano
G
Nanni
Patrizia
P
Lollini
Pier-Luigi
PL
Curti
Antonio
A
Manara
Maria Cristina
MC
Benini
Stefania
S
Bernard
Alain
A
Picci
Piero
P
D000071443:12E7 Antigen; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006412:Hematopoietic Stem Cells; D006801:Humans; D012512:Sarcoma, Ewing / Q000188:drug therapy*
D000071443:12E7 Antigen; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D004317:Doxorubicin