Immunomedics develops new immunoconjugates for cancer chemotherapy

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. This study was supported in part by a grant from the Small Business Innovation Research Program of the National Cancer Institute.

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.

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% was observed with hPAM4-SN-38 treatment.

Cynthia Sullivan, president and CEO of Immunomedics, said: “We have 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.”