Primezone Media Network
April 14, 2008
SAN DIEGO -- Immunomedics, Inc, a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other serious diseases, today announced that results presented at the 2008 Annual Meeting of AACR in San Diego, CA, demonstrated that pretargeting radioimmunotherapy (RAIT) with a trivalent bispecific monoclonal antibody (bsMAb), when compared to a directly radiolabeled antibody, improved anti-tumor responses with less toxicity in a human non-Hodgkin's lymphoma model.
"We are encouraged by these preclinical results, which validated the potential of pretargeting RAIT in cancer treatments," said Cynthia L. Sullivan, President and CEO of Immunomedics. This cutting edge technology was developed by IBC Pharmaceuticals, Inc., a majority-owned subsidiary of Immunomedics.
In traditional RAIT, radioisotopes are linked directly to antibodies and are delivered together to tumor targets. Pretargeting RAIT involves a separate delivery of radioisotope, which is given after the administration of a bsMAb. Because of the time lag, when the therapeutic isotope is administered, the amount of bsMAb is reduced in the blood and normal tissues, and is preferentially bound to the tumor. This allows a higher delivery of radiation to the tumors without increased toxicity to normal tissues.
Mice bearing human non-Hodgkin's lymphoma transplants were used in this study. For pretargeting, TF4, a trivalent bsMAb with dual binding to the CD20 antigen and monovalent binding to a histamine-succinyl-glycine (HSG) hapten was used. Targeted radiation was delivered as the yttrium-90-labeled HSG-peptide. This was compared to yttrium-90-labeled veltuzumab, a direct targeting anti-CD20 humanized monoclonal antibody developed by Immunomedics.
Results showed that whole body clearance of yttrium-90 from the pretargeted group was much more rapid than the direct targeting group. In pretargeting, less than 10% of the injected dose remained in the body within a few hours. In contrast, the direct targeting group had over 50% of radioactivity in the body at 2 days. At the same time, the levels of radioactivity in tumors were higher in the pretargeted than in the direct-targeting animals. In pretargeting, maximum tumor uptake occurs within 1 h, with tumor/blood ratios greater than 20:1 at 3 hours. The tumor uptake with the yttrium-90-labeled veltuzumab was less than the blood level for more than 3 days.
Pretargeted yttrium-90 labeled HSG-peptide was highly effective in controlling tumor growth and eliciting cures in animals with well-established lymphoma transplants, even at the low dose of 0.15 mCi. At the highest dose tested of 0.70 mCi, 90% of the tumors were completely ablated, with no severe treatment-related toxicity observed over 20 weeks. While tumors partially responded to doses of 0.15 mCi of the yttrium-90-labeled veltuzumab, most tumors quickly re-grew. Moreover, severe toxicity was observed in 8/20 animals within the first 3 weeks, and no cures were noted.
About Pretargeting Radioimmunotherapy
Pretargeting radioimmunotherapy (RAIT) uses a 'two-step' approach in the delivery of therapeutic isotope. A humanized bispecific monoclonal antibody (bsMAb), with one arm that recognizes a tumor-associated antigen and another arm that recognizes a peptide that carries a therapy agent, is given as a first injection. When non-tumor-bound bsMAb has substantially cleared non-target tissues and bsMAb has reached a maximum level in the tumor, the bsMAb-recognizable therapy agent is given. The latter agent either targets the bsMAb localized at the tumor, or it is rapidly cleared through urine via the kidneys. Pretargeting RAIT is an attractive potential alternative to traditional RAIT, because the delivery of therapeutic isotope is rapid and is separated from the long antibody delivery process, thereby reducing radiation exposure to normal tissues.
About Immunomedics
Immunomedics is a New Jersey-based biopharmaceutical company focused on the development of monoclonal, antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases. We have developed a number of advanced proprietary technologies that allow us to create humanized antibodies that can be used either alone in unlabeled or "naked" form, or conjugated with radioactive isotopes, chemotherapeutics or toxins, in each case to create highly targeted agents. Using these technologies, we have built a pipeline of therapeutic product candidates that utilize several different mechanisms of action. We have exclusively licensed our lead product candidate, epratuzumab, to UCB for the treatment of all autoimmune disease indications worldwide. Epratuzumab's most advanced clinical testing is for the treatment of systemic lupus erythematosus (SLE) and in non-Hodgkin's lymphoma (NHL). At present, there is no cure for lupus and no new lupus drug has been approved in the U.S. in the last 40 years. We have retained the rights for epratuzumab in oncology indications, and are advancing trials in lymphoma and in childhood acute lymphoblastic leukemia in cooperation with National Cancer Institute Study Groups. In addition, the Company is conducting clinical trials with intravenous veltuzumab in patients with NHL and immune thrombocytopenic purpura, subcutaneous veltuzumab in NHL and chromic lymphocytic leukemia (CLL), 90Y-epratuzumab for the therapy of patients with lymphoma, 90Y-hPAM4 combined with gemcitabine for pancreatic cancer therapy, and milatuzumab (anti-CD74 humanized antibody) as a therapy for patients with multiple myeloma, NHL, and CLL.
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