AS1409
AS1409 (huBC1-huIL12)
AS1409 is a fusion protein combining the anti-tumour cytokine IL-12, with the tumour-targeting antibody BC1. AS1409 has entered a phase I trial in renal (kidney) cancer and melanoma.
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huBC1 binds to a fibronectin splice variant (ED-B) that is highly expressed in the extracellular matrix and blood vessels of tumour tissues but has very restricted distribution in normal tissues.
IL-12 is a cytokine with both cytotoxic and anti-angiogenic activity that has demonstrated anti-cancer effects in clinical trials with renal cancer and melanoma patients. However, the systemic application of IL-12 has been limited by its toxicity.
AS1409 is designed to deliver IL-12 directly to the tumour vasculature via the antibody BC1 and to evoke a localised immune cascade, whilst minimising the systemic side effects of IL-12.
Preclinical studies
A surrogate molecule, huBC1-muIL12, has shown potent antitumour activity in several xenograft tumour models.
Both the huBC1 antibody and the huBC1-huIL12 fusion protein have been shown to bind to ED-B fibronectin in renal carcinoma and metastatic melanoma tissue samples, where there is widespread expression of ED-B containing fibronectin.
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