MedImmune’s Oncology group announced preclinical results showing that MEDI-573, a targeted monoclonal antibody, broadly suppresses pathways that have been shown to play a critical role in the development and progression of many solid tumours.

MEDI-573 is the only human monoclonal antibody (MAb) currently under clinical development that neutralizes both Insulin-like Growth Factor (IGF)-I and IGF-II, growth hormones that regulate cell growth, survival, differentiation, and transformation (i.e., the process of acquiring cancerous characteristics). This MedImmune compound specifically inhibits IGF signalling through two important pathways: IGF-1R and IR-A (insulin receptor isoform A).

Unlike the other IGF-1R-targeting MAbs in development that target only IGF-1R, MEDI-573 neutralizes both the receptors IGF-1R and IR-A as well as their hybrid receptors.  In addition, MEDI-573 spares the insulin receptor isoform B (IR-B), which interacts with insulin and is crucial for the metabolism of glucose – the body’s main source of energy. Therapies that affect IR-B have been shown to raise or drop blood sugar levels, both of which can cause serious health problems. Preliminary data from MedImmune’s first-time-in-human study suggest that MEDI-573 does not alter glucose homeostasis.

“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 Jin Gao, PhD, Scientist II in Oncology Research at MedImmune and lead author of the study.  “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.”

This in vivo study demonstrates that MEDI-573 inhibited the activity of IGF signalling pathways in mice implanted with two different tumour cell lines, C32 and P12.  In this study, 86% and 91% Tumour Growth Inhibition (TGI) was achieved in mice treated with 30 or 60 mg/kg MEDI-573, respectively.

In addition, the study found that using 18F-FDG-PET imaging (fluorodeoxyglucose positron emission tomography) may provide a non-invasive way to monitor treatment response within a few days of starting treatment, prior to documented reductions in the tumour size.

IGF signalling pathways play an important role in the development and progression of many solid tumours. Disruption of IGF signalling pathways by neutralizing IGF-I and IGF-II ligands enables broader suppression of the IGF system and is a novel strategy for the treatment of solid tumours. MEDI-573 is a dual-targeting fully human monoclonal antibody that neutralizes IGF-I and IGF-II ligands. In preclinical studies, this neutralization was shown to block IGF-1R, IGF-1R/ IR-A hybrid and IR-A signalling, which inhibited cancer cell growth. MEDI-573 is in phase 1 clinical evaluation in patients with advanced solid tumours and is planned to begin phase 2 studies this year.

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