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tTF-NGR - Tumour-targeted fusion protein for vascular blockade in cancer therapy

tTF-NGR is a fusion protein for targeted tumour therapy via vascular occlusion. Find out everything about the mechanism of action, application in cancer and current studies such as TRABTRAP.

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tTF-NGR (truncated Tissue Factor)
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Wissenswertes über "tTF-NGR (truncated Tissue Factor)"

tTF-NGR is a fusion protein for targeted tumour therapy via vascular occlusion. Find out everything about the mechanism of action, application in cancer and current studies such as TRABTRAP.

tTF-NGR is a biotechnologically produced fusion proteinfusion protein that specifically targets tumour-associated vessels. It combines two functional units:

  • tTF (truncated tissue factor): a truncated form of human tissue factor that can activate blood clotting

  • NGR peptide (Asn-Gly-Arg): a tumour-homing sequence that binds specifically to CD13-positive endothelial cells

selectively induce microthrombosis in tumour vessels, thereby interrupting the tumour's blood supply and cutting off the cancer cells from nutrient replenishment.

  • Targeted binding: The NGR peptide binds specifically to CD13, a molecule that is increasingly expressed on the vascular walls of tumour-associated endothelial cells.

  • Activation of blood coagulation: After binding, the tTF part activates the external coagulation cascade - but only in CD13-positive tissue.

  • Vascular occlusion: local microthromboses develop, leading to ischemia and tumour cell death - without causing significant damage to surrounding healthy tissue.

    • targeted antiangiogenic therapy for difficult-to-treat tumours, in particular:

    • Soft tissue sarcomas (e.g. in the TRABTRAP study in combination with trabectedin)

    • Colorectal carcinoma

    • Hepatocellular carcinoma

    tumour regression while maintaining systemic tolerability.

  • Phase I and II studies, tTF-NGR could be safely administered and showed biological activity.

  • TRABTRAP trial (phase III) is investigating the combination of tTF-NGR with trabectedin in CD13-positive soft tissue sarcoma in second-line therapy.

    • Advantages:

    • Challenges:

      • thrombosis in sensitive tissue must be controlled

      innovative drug approach that uses vascular occlusion therapeutically to selectively starve tumours. Thanks to its tumour selectivity, it offers the chance of effective yet tolerable therapies for aggressive cancers.

      Literature references:

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    Verwandte Suchbegriffe: tTF-NGR + truncated Tissue Factor + tTF NGR + tTFNGR + tTF

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