Preclinical Results Presented at the 102nd Annual Meeting of AACR
Development of a Dendritic Cell Vaccine for Cancer Therapy also Reported
ORLANDO, Fla., April 4, 2011 (GLOBE NEWSWIRE) -- Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases, today announced results from a preclinical study of C2-2b-2b, a new protein construct created by the Company's proprietary Dock-and-Lock method (DNL) for protein engineering. C2-2b-2b is an immunocytokine comprising 4 molecules of interferon-alpha-2b (IFNα2b) fused to the humanized antibody, IMMU-114, that targets the HLA-DR antigen.
IFNα2b has been used in the treatment of patients with a variety of blood cancers, including multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), hairy cell leukemia, and chronic myeloid leukemia. However, its therapeutic potential is limited by its short circulating half-life and systemic toxicity. Fusion of IFNα2b to a monoclonal antibody improves solubility and stability, and markedly increases its circulating half-life. In addition to allowing less frequent and lower dosing, targeting of IFNα2b to tumor sites using a tumor-directed antibody can reduce systemic concentrations and increase local concentration and tumor retention of IFNα2b, thereby improving the therapeutic index. Increased tumor concentrations of IFNα2b can augment its direct anti-proliferative, apoptotic and anti-angiogenic activity, as well as prime an anti-tumor immune response.
The objective of this study was to evaluate the in-vitro and in-vivo anti-tumor activities of C2-2b-2b in myelomas, lymphomas and leukemias. C2-2b-2b inhibited a panel of 20 of 22 cell lines tested and in most cases was more effective than a mixture containing IMMU-114 and IFNα. A given cell's responsiveness to the DNL construct was found to depend on HLA-DR expression or density and its sensitivity to IFNα and IMMU-114. C2-2b-2b was remarkably potent in vivo, where a single low dose effectively eliminated advanced human NHL and myeloma tumors in mice. These results suggest that C2-2b-2b might be useful in the treatment of various HLA-DR-expressing hematopoietic malignancies.
Commenting on these results, Cynthia L. Sullivan, President and CEO, stated: "C2-2b-2b is the third antibody-interferon conjugate we have created using DNL and the most potent immunocytokine in our portfolio. The presence of HLA-DR in a broad range of blood cancers has also made C2-2b-2b an attractive candidate for further development."
The generation of DNL-derived antibody-cytokine conjugates has previously been reported by the Company (www.immunomedics.com/news_pdf/2008_PDF/PR04162008.pdf ).
Dendritic Cell Vaccine
The development of a dendritic-cell vaccine was reported in a separate presentation earlier at the same conference. Dendritic cells (DCs) are immune cells that stimulate B cells and T cells to mount specific antibody and cellular immune responses against cancers or infectious diseases. They express high levels of CD74, which is the target of milatuzumab, the Company's proprietary humanized antibody currently in multiple clinical trials for the treatment of NHL, chronic lymphocytic leukemia and multiple myeloma.
The potential of using milatuzumab as a carrier for the delivery of cancer markers to immune cells, such as DCs, in order to trigger an immune response against the cancer, thereby serving as a cancer vaccine, was investigated in this preclinical study. The cancer marker selected in this study was carcinoembryonic antigen (CEA), which is expressed by a large percentage of solid cancers, such as colorectal, breast, and lung cancers.
A fusion protein, milatuzumab-Fab-A3B3, was constructed by linking the Fab fragment of milatuzumab to the A3B3 domain of CEA. The fusion protein was found to bind efficiently to human antigen-presenting cells (APCs) but not T cells. Unlike milatuzumab, it did not reduce myeloid DCs in human peripheral blood mononuclear cells or suppress T-cell proliferation in allogeneic mixed leukocyte reaction. More importantly, DCs loaded with milatuzumab-Fab-A3B3 were more efficient in inducing CEA-specific immune responses than DCs loaded with CEA.
These results indicate that cross-presentation of a tumor antigen by DCs can be enhanced by targeting the CD74 antigen on DCs, and suggest that the Fab fragment of milatuzumab may be a promising, novel tool for use as a cancer vaccine, because it enhances the cross-presentation of antigens without significant cytotoxicity and functional alteration on APCs.
Immunomedics is a New Jersey-based biopharmaceutical company primarily 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, cytokines 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 also have a majority ownership in IBC Pharmaceuticals, Inc., which is developing a novel Dock-and-Lock (DNL) methodology with us for making fusion proteins and multifunctional antibodies, and a new method of delivering imaging and therapeutic agents selectively to disease, especially different solid cancers (colorectal, lung, pancreas, etc.), by proprietary, antibody-based, pretargeting methods. We believe that our portfolio of intellectual property, which includes approximately 170 patents issued in the United States and more than 400 foreign patents, protects our product candidates and technologies. For additional information on us, please visit our website at . The information on our website does not, however, form a part of this press release.
This release, in addition to historical information, may contain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding clinical trials, out-licensing arrangements (including the timing and amount of contingent payments), forecasts of future operating results, and capital raising activities, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, risks associated with new product development (including clinical trials outcome and regulatory requirements/actions), our dependence on our licensing partners for the further development of epratuzumab for autoimmune indications and veltuzumab for non-cancer indications, competitive risks to marketed products and availability of required financing and other sources of funds on acceptable terms, if at all, as well as the risks discussed in the Company's filings with the Securities and Exchange Commission. The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.
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