- Study Reported at the 2012 Annual Meeting of the American Association for Cancer Research (AACR)
- Preclinical Study of Ranpirnase-Based Therapeutics for Breast Cancer Also Presented
CHICAGO, IL, USA I April 3, 2012 I Immunomedics, Inc. (Nasdaq:IMMU – News), 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 presented results from two preclinical studies on the development of Dock-and-Lock (DNL) derived novel therapeutic agents targeting solid tumors, including renal cell carcinomas (RCC).
RCC constitutes approximately 90% of kidney cancers. About one third of patients diagnosed with RCC have advanced or metastatic disease. These patients face a poor prognosis, because the cancer is resistant to conventional chemotherapy or radiotherapy. Resistance to therapy develops when cancer cells activate a communication system known as the insulin-like growth factor-I (IGF-I) to interact with their environment. Clinically, expression of IGF-I receptor (IGF-IR) in RCC is associated with poor long-term patient survival, particularly among patients with high-grade tumors.
The Company has previously developed hR1, a humanized anti-IGF-1R monoclonal antibody that binds to multiple tumor types, including RCC, resulting in moderate inhibition of cell growth. To enhance the anti-tumor activity of hR1, two novel multivalent/multifunctional agents, 1R-2b and Hex-hR1, were created using the Company’s patented DNL conjugation technology. 1R-2b is composed of an intact hR1 antibody with 2 molecules of interferon-α2b (IFN-α2b) attached to it, whereas Hex-hR1 is comprised of 6 antigen-binding regions of hR1 tethered onto a common crystallizable region of the antibody.
Both hR1-derived agents displayed cell binding activity comparable to their parental antibody. However, Hex-hR1 could effectively down-regulate IGF-IR at concentrations 10-fold lower than hR1. All 3 agents significantly inhibited the growth of two different RCC cell lines and demonstrated a synergistic interaction with temsirolimus, an approved drug for the treatment for RCC, at concentrations as low as 1 nanomolar (nM) for Hex-hR1, 2.6 nM for 1R-2b, and 10 nM for hR1.
These in vitro findings suggest that the two novel DNL agents derived from hR1 have enhanced anti-renal cell carcinoma activities, which can be further improved with the addition of temsirolimus. Therapeutic efficacy studies are currently underway to determine if these in vitro observations will translate to the in vivo setting.
The second group of DNL agents presented at the same AACR meeting was based on ranpirnase (Rap), an amphibian ribonuclease. Ribonucleases are naturally-occurring enzymes that degrade ribonucleic acids, which can cause cell death by inhibiting protein synthesis. The Company has previously demonstrated that the potency of Rap can be enhanced by linking it to tumor-targeting antibodies. (For more information, please refer to the Company’s press release at www.immunomedics.com/pdfs/news/2010/PR04212010.pdf).
In this preclinical study, Rap was conjugated by DNL to hRS7, an internalizing, humanized, anti-TROP-2 antibody owned by the Company. TROP-2 is a cell-surface receptor expressed by many human tumors, such as cancers of the breast, cervix, colon and rectum, lung, pancreas, and prostate. The resulting agent, E1-Rap, which contains 4 copies of Rap, was evaluated as a potential therapeutic for breast cancer.
In a panel of 7 human breast cancer cell lines, Rap and hRS7 showed negligible in vitro cytotoxicity when used separately or in combination. Five of the 7 cell lines examined expressed high to moderate levels of TROP-2. E1-Rap exhibited potency at the nanomolar or sub-nanomolar level in these cell lines, but was not very effective in inhibiting the proliferation of a more aggressive cell line, which has low level of TROP-2 expression, or of the TROP-2-negative line.
These results warrant the further development of E1-Rap as a new therapeutic candidate for TROP-2-expressing breast and other solid tumors.
"We are pleased with these encouraging preclinical results," remarked Cynthia L. Sullivan, President and Chief Executive Officer. "We look forward to continue further developing these agents for the therapy of a wide variety of human cancers, extending our extensive pipeline of anticancer agents."
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 (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 191 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 www.immunomedics.com. The information on our website does not, however, form a part of this press release.
SOURCE: Immunomedics
Post Views: 48
- Study Reported at the 2012 Annual Meeting of the American Association for Cancer Research (AACR)
- Preclinical Study of Ranpirnase-Based Therapeutics for Breast Cancer Also Presented
CHICAGO, IL, USA I April 3, 2012 I Immunomedics, Inc. (Nasdaq:IMMU – News), 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 presented results from two preclinical studies on the development of Dock-and-Lock (DNL) derived novel therapeutic agents targeting solid tumors, including renal cell carcinomas (RCC).
RCC constitutes approximately 90% of kidney cancers. About one third of patients diagnosed with RCC have advanced or metastatic disease. These patients face a poor prognosis, because the cancer is resistant to conventional chemotherapy or radiotherapy. Resistance to therapy develops when cancer cells activate a communication system known as the insulin-like growth factor-I (IGF-I) to interact with their environment. Clinically, expression of IGF-I receptor (IGF-IR) in RCC is associated with poor long-term patient survival, particularly among patients with high-grade tumors.
The Company has previously developed hR1, a humanized anti-IGF-1R monoclonal antibody that binds to multiple tumor types, including RCC, resulting in moderate inhibition of cell growth. To enhance the anti-tumor activity of hR1, two novel multivalent/multifunctional agents, 1R-2b and Hex-hR1, were created using the Company’s patented DNL conjugation technology. 1R-2b is composed of an intact hR1 antibody with 2 molecules of interferon-α2b (IFN-α2b) attached to it, whereas Hex-hR1 is comprised of 6 antigen-binding regions of hR1 tethered onto a common crystallizable region of the antibody.
Both hR1-derived agents displayed cell binding activity comparable to their parental antibody. However, Hex-hR1 could effectively down-regulate IGF-IR at concentrations 10-fold lower than hR1. All 3 agents significantly inhibited the growth of two different RCC cell lines and demonstrated a synergistic interaction with temsirolimus, an approved drug for the treatment for RCC, at concentrations as low as 1 nanomolar (nM) for Hex-hR1, 2.6 nM for 1R-2b, and 10 nM for hR1.
These in vitro findings suggest that the two novel DNL agents derived from hR1 have enhanced anti-renal cell carcinoma activities, which can be further improved with the addition of temsirolimus. Therapeutic efficacy studies are currently underway to determine if these in vitro observations will translate to the in vivo setting.
The second group of DNL agents presented at the same AACR meeting was based on ranpirnase (Rap), an amphibian ribonuclease. Ribonucleases are naturally-occurring enzymes that degrade ribonucleic acids, which can cause cell death by inhibiting protein synthesis. The Company has previously demonstrated that the potency of Rap can be enhanced by linking it to tumor-targeting antibodies. (For more information, please refer to the Company’s press release at www.immunomedics.com/pdfs/news/2010/PR04212010.pdf).
In this preclinical study, Rap was conjugated by DNL to hRS7, an internalizing, humanized, anti-TROP-2 antibody owned by the Company. TROP-2 is a cell-surface receptor expressed by many human tumors, such as cancers of the breast, cervix, colon and rectum, lung, pancreas, and prostate. The resulting agent, E1-Rap, which contains 4 copies of Rap, was evaluated as a potential therapeutic for breast cancer.
In a panel of 7 human breast cancer cell lines, Rap and hRS7 showed negligible in vitro cytotoxicity when used separately or in combination. Five of the 7 cell lines examined expressed high to moderate levels of TROP-2. E1-Rap exhibited potency at the nanomolar or sub-nanomolar level in these cell lines, but was not very effective in inhibiting the proliferation of a more aggressive cell line, which has low level of TROP-2 expression, or of the TROP-2-negative line.
These results warrant the further development of E1-Rap as a new therapeutic candidate for TROP-2-expressing breast and other solid tumors.
"We are pleased with these encouraging preclinical results," remarked Cynthia L. Sullivan, President and Chief Executive Officer. "We look forward to continue further developing these agents for the therapy of a wide variety of human cancers, extending our extensive pipeline of anticancer agents."
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 (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 191 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 www.immunomedics.com. The information on our website does not, however, form a part of this press release.
SOURCE: Immunomedics
Post Views: 48
