Data from CD62L as a Therapeutic Target in Chronic Lymphocytic Leukemia

<div>Abstract<p><b>Purpose:</b> Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL.</p><p><b>Experimental Design:</b> The expression of 71 cell surface molecules was examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture. The most highly upregulated marker, CD62L, was examined further for expression on CD5⁺/CD19⁺ CLL cells <i>in vitro</i> and in lymph node and bone marrow biopsies. The prosurvival role of CD62L was examined using a functional blocking antibody and therapeutic potential evaluated by comparison with current chemotherapy agents.</p><p><b>Results:</b> Blocking CD62L resulted in apoptosis of CLL cells but not PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of coculturing CLL cells with bone marrow stromal cells or endothelial cells does not protect CLL cells from anti-CD62L–related toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L <i>in vitro</i> produced an additive effect both with and without stromal cells.</p><p><b>Conclusion:</b> This is the first reported data showing that blocking the activation and homing marker, CD62L, regulates CLL cell survival <i>in vitro.</i> These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to patients with CLL receiving current standard chemotherapy protocols. <i>Clin Cancer Res; 19(20); 5675–85. ©2013 AACR</i>.</p></div>