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NGR-hTNF

NGR-hTNF is a novel therapeutic agent for solid tumours that specifically targets tumour blood vessels. It originates from the fusion of the CNGRCG tumour homing peptide and of human tumour necrosis factor α (hTNF).

The CNGRCG peptide selectively targets tumour blood vessels by binding to an isoform of the CD13 (also named aminopeptidase N) receptor, which is present on endothelial cells of the tumour vasculature, while sparing the CD13-expressing molecules of normal tissues.

The fusion of hTNF to the CNGRC peptide concentrates hTNF onto the tumour site, thus allowing NGR-hTNF to exert its pharmacological effects at concentrations sufficiently low as to avoid inducing counter-regulatory effects such as release into the circulation of soluble TNF-receptor (TNFR) and recruitment at the tumour site of bone-marrow derived cells with pro-angiogenic and pro-tumourigenic activity.

In vivo binding of NGR-hTNF to both CD13 and TNFR on endothelial cells of tumour vessels induces increased vascular permeability, thereby improving the effectiveness of chemotherapy agents administered in combination, as well as endothelial cell apoptosis, ultimately impairing tumour growth.

NGR-hTNF is currently investigated in a pivotal Phase III trial for the treatment of malignant pleural mesothelioma, as well as in four randomised Phase II trials in four types of solid tumours, as monotherapy or in combination with chemotherapeutic regimens.

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