SAN DIEGO, CA, USA I December 5, 2012 I Immunomedics, Inc. (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 reported the development of two bispecific, hexavalent antibodies created using the Company’s patented DOCK-AND-LOCK(TM) (DNL(TM)) conjugation technology for targeted therapies of various epithelial cancers. Results from this preclinical study were presented at IBC’s 9th Annual Antibody Therapeutics Conference in San Diego, CA.
DNL is a protein engineering platform technology for the rapid and facile creation of a wide variety of active biological agents designed for biotechnological and biomedical applications. The basis of DNL is in the natural interaction between two peptides called DDD (Docking and Dimerization Domain) and AD (Anchoring Domain). They are used as building blocks for the attachment of precursor proteins, or other entities, to become DNL-modules. When mixed together, the two modules bind with each other exclusively and spontaneously to form a complex, a process known as "docking". Once "docked", the complex is "locked" by disulfide bridges into a stably-tethered structure. The outcome of DNL is a new and stable agent, produced in a quantitative manner, which retains the full biological activities of its individual components.
The precursor antibodies used in this preclinical study were hR1, the Company’s proprietary humanized antibody against the type I insulin-like growth factor receptor (IGF-1R), hRS7, a humanized antibody targeting the trophoblast cell-surface marker (TROP-2), and hMN-15, a proprietary humanized antibody that recognizes the carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6).
The expression of IGF-1R, TROP-2 and CEACAM6 are elevated in diverse epithelial cancers, making them attractive targets for antibody-based cancer therapy. The use of two distinct monoclonal antibodies in combination to improve efficacy has produced promising results in some early clinical studies. However, one multispecific antibody could be more efficient and economical than infusing 2 or more antibodies. Furthermore, targeting different antigens may have complementary, improved effects. Additional binding arms should also enhance avidity, reduce off-rates, and increase anti-target activity.
Two bispecific antibodies, designated as 1R-(E1)-(E1) and 1R-(15)-(15), were generated using an intact hR1 attached with four Fab fragments of hRS7 and hMN-15, respectively. Their therapeutic potential for epithelial cancers was evaluated on three breast cancer cell lines of varying invasiveness, and one pancreatic cancer cell line.
At 50 mg/mL, 1R-(E1)-(E1) reduced the invasion of a breast cancer cell line to less than 10% of the untreated control, but had no effect on a more invasive cell line under the same conditions. However, at 200 nM, it inhibited anchorage-independent growth of the more invasive cell line, with a statistically significant difference when compared with samples treated with parental antibodies at the same concentrations. Furthermore, cells treated with the bispecific antibody produced fewer and much smaller colonies, the largest size of which was less than 1/10 of the untreated cells. For 1R-(15)-(15), it effectively reduced the invasion of a pancreatic cancer cell line, but had no apparent effect on the less invasive breast cancer cell line.
In remarks by Company President and Chief Executive Officer, Cynthia L. Sullivan: "We are pleased to have developed these two bispecific hexavalent antibodies for targeted therapy of solid cancers. Both DNL-constructs showed improved activity over their parental antibodies in controlling the spread and invasiveness of human breast or pancreatic cancer cells in culture."
About Immunomedics
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(TM) (DNL(TM)) method 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 209 active patents 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 www.immunomedics.com. The information on our website does not, however, form a part of this press release.
SOURCE: Immunomedics
Post Views: 697
SAN DIEGO, CA, USA I December 5, 2012 I Immunomedics, Inc. (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 reported the development of two bispecific, hexavalent antibodies created using the Company’s patented DOCK-AND-LOCK(TM) (DNL(TM)) conjugation technology for targeted therapies of various epithelial cancers. Results from this preclinical study were presented at IBC’s 9th Annual Antibody Therapeutics Conference in San Diego, CA.
DNL is a protein engineering platform technology for the rapid and facile creation of a wide variety of active biological agents designed for biotechnological and biomedical applications. The basis of DNL is in the natural interaction between two peptides called DDD (Docking and Dimerization Domain) and AD (Anchoring Domain). They are used as building blocks for the attachment of precursor proteins, or other entities, to become DNL-modules. When mixed together, the two modules bind with each other exclusively and spontaneously to form a complex, a process known as "docking". Once "docked", the complex is "locked" by disulfide bridges into a stably-tethered structure. The outcome of DNL is a new and stable agent, produced in a quantitative manner, which retains the full biological activities of its individual components.
The precursor antibodies used in this preclinical study were hR1, the Company’s proprietary humanized antibody against the type I insulin-like growth factor receptor (IGF-1R), hRS7, a humanized antibody targeting the trophoblast cell-surface marker (TROP-2), and hMN-15, a proprietary humanized antibody that recognizes the carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6).
The expression of IGF-1R, TROP-2 and CEACAM6 are elevated in diverse epithelial cancers, making them attractive targets for antibody-based cancer therapy. The use of two distinct monoclonal antibodies in combination to improve efficacy has produced promising results in some early clinical studies. However, one multispecific antibody could be more efficient and economical than infusing 2 or more antibodies. Furthermore, targeting different antigens may have complementary, improved effects. Additional binding arms should also enhance avidity, reduce off-rates, and increase anti-target activity.
Two bispecific antibodies, designated as 1R-(E1)-(E1) and 1R-(15)-(15), were generated using an intact hR1 attached with four Fab fragments of hRS7 and hMN-15, respectively. Their therapeutic potential for epithelial cancers was evaluated on three breast cancer cell lines of varying invasiveness, and one pancreatic cancer cell line.
At 50 mg/mL, 1R-(E1)-(E1) reduced the invasion of a breast cancer cell line to less than 10% of the untreated control, but had no effect on a more invasive cell line under the same conditions. However, at 200 nM, it inhibited anchorage-independent growth of the more invasive cell line, with a statistically significant difference when compared with samples treated with parental antibodies at the same concentrations. Furthermore, cells treated with the bispecific antibody produced fewer and much smaller colonies, the largest size of which was less than 1/10 of the untreated cells. For 1R-(15)-(15), it effectively reduced the invasion of a pancreatic cancer cell line, but had no apparent effect on the less invasive breast cancer cell line.
In remarks by Company President and Chief Executive Officer, Cynthia L. Sullivan: "We are pleased to have developed these two bispecific hexavalent antibodies for targeted therapy of solid cancers. Both DNL-constructs showed improved activity over their parental antibodies in controlling the spread and invasiveness of human breast or pancreatic cancer cells in culture."
About Immunomedics
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(TM) (DNL(TM)) method 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 209 active patents 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 www.immunomedics.com. The information on our website does not, however, form a part of this press release.
SOURCE: Immunomedics
Post Views: 697
