Mechanism of Action Study on Epratuzumab Also Reported
WASHINGTON, DC, USA I April 10, 2013 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 announced the development of novel T-cell redirecting agents made as DOCK-AND-LOCK(TM) (DNL(TM)) complexes by tethering a single-chain variable fragment (scFv) that binds to CD3 on T cells to different antibody fragments that target tumor antigens. The preclinical study was presented at the 2013 Annual Meeting of the American Association for Cancer Research (AACR).
The use of bispecific antibodies to redirect T cells for the killing of targeted tumor cells has shown considerable promise both preclinically and clinically. The Company has previously reported the generation of (19)-3s, a prototype bispecific antibody that binds to CD19 on B cells and CD3 on T cells, using the Company’s patented DNLTM platform technology. (19)-3s has demonstrated in vitro the ability to direct T cells to destroy CD19-expressing B cells by linking them together. (For more information, please refer to the Company’s press release at www.immunomedics.com/pdfs/news/2012/pr12122012.pdf).
In the current study, (19)-3s was found to be highly effective in vivo. In an animal model of human lymphoma, 6 of the 8 animals that were treated with 43 micrograms of the DNLTM-derived bispecific antibody for five doses remained alive, with 5 of 8 animals tumor-free at the end of the study.
Encouraged by these results, a panel of novel T-cell redirecting bispecific antibodies were created by DNLTM as potential therapeutics for solid malignancies. Three DNLTM complexes, designated (14)-3s, (E1)-3s, and (M1)-3s, were prepared by linking anti-CD3 scFv to humanized antibody fragments with specificity for CEACAM5, TROP-2, and PAM4-antigen, respectively. All three biomarkers are expressed in many solid tumors. (14)-3s and (E1)-3s both exhibited anti-tumor activity in animal models of human colonic and pancreatic cancers, respectively.
“The modular nature of DNLTM has allowed us to rapidly produce a large number of complexes as T-cell redirecting agents for various malignancies,” commented Cynthia L. Sullivan, President and Chief Executive Officer. “We are currently evaluating the in vitro and in vivo properties of these DNLTM complexes in cognate solid tumors,” Ms. Sullivan added.
At the same AACR meeting, a study on the mechanism of action of epratuzumab was also presented.
Epratuzumab is a humanized anti-CD22 antibody currently in clinical development for B-cell lymphoma and systemic lupus erythematosus, an autoimmune disease. Although epratuzumab is capable of depleting on average 35% of circulating B cells in patients, its in vivo mechanism of action, especially its involvement in regulating B-cell antigen receptor (BCR) signaling, remains poorly understood.
In this preclinical study, peripheral blood mononuclear cells from either healthy donors or lupus patients with flares were incubated with epratuzumab, and the relative surface levels of CD22 and selected BCR regulators, including CD19, CD21, and CD79b, were analyzed.
Epratuzumab promptly induced the transfer of CD22 and the 3 BCR-associated regulators from B cells to other white blood cells such as monocytes, natural killer cells and granulocytes, a process known as trogocytosis. The transfer is mediated through the interaction of the fragment crystalline (Fc) region of CD22-bound epratuzumab and the Fc receptors on the effector cells.
“This study revealed a previously unknown, and potentially important, mechanism of action of epratuzumab,” remarked Cynthia L. Sullivan, President and Chief Executive Officer. “Whether the observed trogocytosis could be correlated with the depletion of malignant B cells in lymphoid tissues is currently under investigation,” added Ms. Sullivan.
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 220 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 http://www.immunomedics.com/“>www.immunomedics.com. The information on our website does not, however, form a part of this press release.
SOURCE: Immunomedics
Post Views: 171
Mechanism of Action Study on Epratuzumab Also Reported
WASHINGTON, DC, USA I April 10, 2013 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 announced the development of novel T-cell redirecting agents made as DOCK-AND-LOCK(TM) (DNL(TM)) complexes by tethering a single-chain variable fragment (scFv) that binds to CD3 on T cells to different antibody fragments that target tumor antigens. The preclinical study was presented at the 2013 Annual Meeting of the American Association for Cancer Research (AACR).
The use of bispecific antibodies to redirect T cells for the killing of targeted tumor cells has shown considerable promise both preclinically and clinically. The Company has previously reported the generation of (19)-3s, a prototype bispecific antibody that binds to CD19 on B cells and CD3 on T cells, using the Company’s patented DNLTM platform technology. (19)-3s has demonstrated in vitro the ability to direct T cells to destroy CD19-expressing B cells by linking them together. (For more information, please refer to the Company’s press release at www.immunomedics.com/pdfs/news/2012/pr12122012.pdf).
In the current study, (19)-3s was found to be highly effective in vivo. In an animal model of human lymphoma, 6 of the 8 animals that were treated with 43 micrograms of the DNLTM-derived bispecific antibody for five doses remained alive, with 5 of 8 animals tumor-free at the end of the study.
Encouraged by these results, a panel of novel T-cell redirecting bispecific antibodies were created by DNLTM as potential therapeutics for solid malignancies. Three DNLTM complexes, designated (14)-3s, (E1)-3s, and (M1)-3s, were prepared by linking anti-CD3 scFv to humanized antibody fragments with specificity for CEACAM5, TROP-2, and PAM4-antigen, respectively. All three biomarkers are expressed in many solid tumors. (14)-3s and (E1)-3s both exhibited anti-tumor activity in animal models of human colonic and pancreatic cancers, respectively.
“The modular nature of DNLTM has allowed us to rapidly produce a large number of complexes as T-cell redirecting agents for various malignancies,” commented Cynthia L. Sullivan, President and Chief Executive Officer. “We are currently evaluating the in vitro and in vivo properties of these DNLTM complexes in cognate solid tumors,” Ms. Sullivan added.
At the same AACR meeting, a study on the mechanism of action of epratuzumab was also presented.
Epratuzumab is a humanized anti-CD22 antibody currently in clinical development for B-cell lymphoma and systemic lupus erythematosus, an autoimmune disease. Although epratuzumab is capable of depleting on average 35% of circulating B cells in patients, its in vivo mechanism of action, especially its involvement in regulating B-cell antigen receptor (BCR) signaling, remains poorly understood.
In this preclinical study, peripheral blood mononuclear cells from either healthy donors or lupus patients with flares were incubated with epratuzumab, and the relative surface levels of CD22 and selected BCR regulators, including CD19, CD21, and CD79b, were analyzed.
Epratuzumab promptly induced the transfer of CD22 and the 3 BCR-associated regulators from B cells to other white blood cells such as monocytes, natural killer cells and granulocytes, a process known as trogocytosis. The transfer is mediated through the interaction of the fragment crystalline (Fc) region of CD22-bound epratuzumab and the Fc receptors on the effector cells.
“This study revealed a previously unknown, and potentially important, mechanism of action of epratuzumab,” remarked Cynthia L. Sullivan, President and Chief Executive Officer. “Whether the observed trogocytosis could be correlated with the depletion of malignant B cells in lymphoid tissues is currently under investigation,” added Ms. Sullivan.
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 220 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 http://www.immunomedics.com/“>www.immunomedics.com. The information on our website does not, however, form a part of this press release.
SOURCE: Immunomedics
Post Views: 171
