Research: Two new approaches VEGF and hLL1

Two new approaches are under investigation against multiple myeloma in clinical trials at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

A Phase 2 trial with VEGF Trap will assess the drug's ability to slow tumor growth in patients with multiple myeloma. VEGF Trap is a recombinant human fusion protein that binds VEGF, a key molecule in tumor blood-vessel growth (angiogenesis).

A Phase 1 trial of hLL1 (anti-CD74), a humanized monoclonal antibody that has shown significant growth inhibition of multiple myeloma and B-lymphoma cells in preclinical studies, and whose mechanism of action is associated with inducing apoptosis (cell death), will be studied for safety and dosage.

Dr. Ruben Niesvizky, director of NewYork-Presbyterian/Weill Cornell's Multiple Myeloma Program is principal investigator of both studies.

Myeloma growth is highly dependent on VEGF (vascular endothelial growth factor) and that blood-vessel growth (angiogenesis) is a fundamental aspect of myeloma tumor growth.

VEGF Trap works by binding VEGF more tightly than the body's own receptors that mediate the angiogenic activity of VEGF.

The drug hLL1 (IMMU-115) represents the first antibody exploiting the high expression of the CD74 molecule (an invariant chain marker associated with HLA antigens) in myeloma cells. This molecule not only plays a role in immunity, but has also been shown to have direct signaling effects in hematopoietic tumors. NewYork-Presbyterian/Weill Cornell is the first to begin evaluation of this new antibody as a therapy for any disease.

The drug hLL1 is developed by Immunomedics of Morris Plains, N.J.; the company is funding the study of its drug. VEGF Trap is being developed in a collaboration between Regeneron Pharmaceuticals of Tarrytown, N.Y. and Sanofi-Aventis USA, of Bridgewater, New Jersey; the study is sponsored by the National Cancer Institute's Cancer Therapy Evaluation Program (NCI/CTEP) under a Clinical Trials Agreement between Sanofi-Aventis and NCI; and conducted under the NCI's Division of Cancer Treatment and Diagnosis Investigational New Drug Application for VEGF Trap.

The Multiple Myeloma Program at NewYork-Presbyterian/Weill Cornell, one of the three largest such centers in the U.S., takes an aggressive and multidisciplinary approach-offering programs for transplants, vaccine development and drugs, as well as clinical research trials for all stages of the disease. The Myeloma Program is also enrolling for other investigational drug therapies.

Co-investigators for the VEGF Trap study include NewYork-Presbyterian/Weill Cornell's Drs. Jia Ruan, Roger Pearse and Morton Coleman; NewYork-Presbyterian/Columbia's Ajai Chari; and investigators representing the other members of the New York Consortium. Statistical analysis will be provided by Weill Cornell's Dr. Madhu Mazumdar. Co-investigators for the hLL1 study include Weill Cornell's Drs. Scott Ely and John Leonard.