The Epitope Targeted by Apoptosis-Inducing ICAM-1 Antibody B11 Is Highly Expressed in Multiple Myeloma.

Abstract 4897

Complex adhesive and non-cognate interactions participate in multiple myeloma disease progression, resistance to apoptosis, and development of drug resistance. In spite of significant recent attempts to develop new drug classes targeting both myeloma and its microenvironment, multiple myeloma remains an incurable disease warranting development of more effective therapies. Applying novel combined target and drug discovery methodology we isolated a human tumor cell apoptosis-inducing antibody (IgG B11) targeting ICAM-1, as previously described. ICAM-1 is a cell adhesion molecule strongly implicated in myeloma pathophysiology, both regarding bone marrow stromal cell mediated disease progression and cell adhesion mediated drug resistance. We here characterize B11 epitope expression by multicolor FACS analysis in 25 patients investigated for multiple myeloma referred to Department of Hematology, Lund University Hospital, Lund, Sweden and 5 healthy controls. The B11 epitope was highly expressed in plasma cells in 5 of 5 patients with myeloma and in 1 of 1 patient with AL (light chain) amyloidosis. A comprehensive preclinical program assessing IgG B11 anti-myeloma activity and evaluating IgG B11 safety has been conducted. Based on these studies, and having received an investigational new drug (IND) approval from the U.S. Food and Drug Administration (FDA), clinical phase I trials with IgG B11 will soon commence.