Novel Dual-Targeting Antibody Strongly Inhibits Tumors in Preclinical Study

A novel dual-targeting human monoclonal antibody has shown promise in preclinical trials where it significantly inhibited the in vivo growth of IGF-I (insulin-like growth factor – I) or IGF-II-driven tumors.

Insulin-like growth factors (IGF), IGF-I and IGF-II, are small polypeptides involved in regulating cell proliferation, survival, differentiation, and transformation. IGF activities are mediated through binding and activation of IGF-1R or insulin receptor isoform A (IR-A). Overexpression of IGF-II and IR-A has been reported in several types of cancer and is proposed as a potential mechanism for cancer cells to develop resistance to IGF-1R–targeting therapy.

The drug developer MedImmune (Gaithersburg, MD, USA) created the human monoclonal antibody MEDI-573 to block IFG receptors overexpression. This novel antibody is capable of simultaneously neutralizing both the receptors IGF-1R and IR-A as well as their hybrid receptors. MEDI-573 does not bind to the insulin receptor isoform B (IR-B), which interacts with insulin and is crucial for glucose metabolism.

A report on MEDI-573 published in the January 18, 2011, online edition of the journal Cancer Research revealed that the antibody inhibited the activity of IGF signaling pathways in mice implanted with two different tumor cell lines, C32 and P12. In this study, 86% and 91% tumor growth inhibition was observed.

"MEDI-573 represents an innovative approach for the treatment of solid tumors with the potential for greater and more consistent inhibition of cancer cell growth than treatments that only target one pathway,” said senior author Dr. Jin Gao, a senior oncology researcher at MedImmune. "The data from our pre-clinical studies are highly promising. Ongoing studies in humans will provide us with a better understanding of the clinical impact of MEDI-573.”

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