Understanding the Mechanism of Action of UV3, an Anti-CD54 Monoclonal Antibody, in the Therapy of Multiple Myeloma
Coleman, Elaine J.
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Multiple myeloma is a hematopoietic malignancy involving the uncontrolled proliferation of a single clone of plasma cells or plasma cell progenitors in the bone marrow. Previously, a monoclonal antibody called UV3, which recognizes human CD54/ICAM-1, was developed for the therapy of multiple myeloma. UV3 is highly effective at treating advanced multiple myeloma in SCID mice with human multiple myeloma xenografts. UV3 does not inhibit homotypic tumor cell adhesion or their adhesion to the bone marrow. UV3 does not induce apoptosis of tumor cells or block cell growth. Previous work evaluating F(ab)'2 fragments of UV3 demonstrated that they were effective in mediating anti-tumor activity, suggesting that other mechanisms also contributed to the anti-tumor activity of UV3. One possibility to explain how UV3 exerts its anti-tumor activity could be that UV3 inhibits the secretion of pro-angiogenic cytokines and molecules, resulting in an inhibition of angiogenesis. To this end, our goal was to evaluate the angiogenic signals from human multiple myeloma cells and determine whether UV3 would interfere with such signals. In addition, we further examined the role of the Fc portion of UV3 in mediating anti-tumor activity. We found that multiple myeloma cell lines secrete some pro-angiogenic cytokines and molecules, and although UV3 may induce a minor anti-angiogenic effect, the Fc portion of UV3 was critical for its anti-tumor activity. In addition, we found that UV3 prolonged the survival of SCID mice with Daudi lymphoma, which suggests UV3 may be effective in treating a variety of hematological malignancies.