PRECLINICAL TESTING OF GALECTIN-3C FOR MULTIPLE MYELOMA

The American Cancer Society expects that there will be more than 20,000 new cases of multiple myeloma (MM) in the US in 2011 and despite the new treatments now available, the median survival rate is only 5 years. Galectin-3C (Gal-3C) is a human lectin involved in cellular processes including cellular differentiation, apoptosis, neoplastic transformation, and metastasis. Gal-3C contains the carbohydrate recognition domain (CRD) of galectin-3 and is thought to act as a dominant negative inhibitor of galectin-3-mediated cross-linking. Gal-3C is a proprietary truncated, inhibitory form of galectin-3. Results showed that in a subcutaneous U266 cell NOD/SCID mouse model of human MM, treatment with an N-terminally truncated form of galectin-3, termed Gal-3C significantly inhibited tumor growth. Furthermore, in vitro data indicated that Gal-3C acts by inhibition of angiogenesis, MM cell migration and invasion, and NF-kB activation. Moreover, Gal-3C facilitates the antitumor activity of bortezomib, a proteasome inhibitor for MM treatment. Gal-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. The delivery of Gal-3C to patients will be via a pump during initial clinical trials. In the long-term, the plan is to develop a formulation of Gal-3C for sustained release to increase survival for patients with MM.