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CD99 Engagement: An Effective Therapeutic Strategy for Ewing Tumors¹

Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, 40136 Italy [K. S., N. B., V. C., M. C. M., S. B., M. S., P. P.]; Istituto di Cancerologia, Università di Bologna, 40126 Bologna, Italy [P. N., P-L. L.]; IST, Istituto Nazionale per la Ricerca sul Cancro-Genova, Unità Satellite di Biotecnologie, 40126 Bologna, Italy [G. N.]; and Unité Institut National de la Santé et de la Recherche Médicale 343, Hôspital de l’Archet, Nice Cedex 3, France [G. B., A. B.]

CD99 is a M_r 32,000 transmembrane molecule that shows a high level of expression on cells of the hemopoietic system as well as on Ewing tumor cells. Within the hematopoietic system, CD99 has been implicated in cell adhesion and cell death, participating in this way in the differentiation of T-cell precursors. In this study, we demonstrate that engagement of CD99 significantly inhibits the in vitro and in vivo growth ability of Ewing tumor cells by delivering an apoptotic stimulus and reducing the malignant potential of these cells. Moreover, we show that anti-CD99 monoclonal antibodies may be advantageously used in association with conventional anticancer agents. These results provide a novel entry site for therapeutic intervention, which may have application in the care of patients with Ewing tumor, and warrant additional studies to clarify the molecular mechanisms activated by CD99 engagement.

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