Immunomedics, a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other serious diseases, has developed three new antibody-drug conjugates aimed at treating pancreatic, colon and lung cancers.
Preclinical results from the immunoconjugates were presented at the 6th International Symposium on Targeted Anticancer Therapies in Bethesda, Md.
According to the Morris Plains, N.J.-based company, all three conjugates involve SN-38, the active metabolite of irinotecan used in chemotherapeutic regimens for colorectal, lung, and pancreatic cancers. Due to its toxicity and poor solubility, SN-38 cannot be given directly to patients. In this study, a previously used SN-38 derivative was redesigned to overcome synthetic and solubility problems.
The new SN-38 derivatives were conjugated to three of the company's proprietary humanized antibodies: labetuzumab for colorectal cancer, hRS7 for lung cancer, and hPAM4 for pancreatic cancer. SN-38 can be selectively delivered to targeted tumors by conjugating it to antibodies, thereby increasing the amount reaching the tumors and minimizing damage to normal tissues and organs, Immunomedics said.
The study results showed that in a lung metastatic model of human colon cancer, therapy with labetuzumab-SN-38 conjugate increased median survival of animals 1.7 to 3-fold to more than 120 days compared to controls. For hRS7-SN-38, therapeutic effects in a human lung cancer model were seen even at 1/10 of the protocol doses for small tumors and the therapeutic specificity was more evident in larger tumors. In a pancreatic cancer model, tumor inhibition of 55 percent was observed with hPAM4-SN-38 treatment.
Cynthia L. Sullivan, president and CEO, said the company has six potential oncology therapeutics in clinical trials: epratuzumab and 90Y-epratuzumab in non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia, veltuzumab in NHL, 90Y-PAM4 in pancreatic cancer, milatuzumab in NHL, chronic lymphocytic leukemia, and multiple myeloma, and 131I-labetuzumab as an adjuvant therapy in metastatic colorectal cancer.
A grant from the Small Business Innovation Research Program of the National Cancer Institute funded part of the study.