VASCULAR TARGETING

VASCULAR TARGETING

'Vascular Targeting’, the leading concept at Philogen, is the targeted delivery of therapeutic agents to newly formed blood vessels at sites of disease. The formation of new blood vessels, or ‘angiogenesis’, is a rare event in the healthy human adult, but is closely associated with various malignant or inflammatory disorders. Newly formed blood vessels are distinct from mature blood vessels at a molecular level, and Philogen has demonstrated that certain proteins, such as splice variants of the extracellular matrix proteins fibronectin and tenascin-C, are specifically expressed in the new vasculature and act as ‘Vascular Markers’ that can be used as targets to deliver a ‘Therapeutic Payload’ (any bioactive agent) to the vicinity of diseased cells. The Therapeutic Payloads that Philogen focuses on are immunomodulatory cytokines.
Philogen’s technology allows for selective delivery of a therapeutic payload attached to a ligand (usually a monoclonal antibody) specific for a ‘Vascular Marker’, and thus enables accumulation of high concentrations of the therapeutic payload at the site of disease, while sparing the patient’s healthy tissues.
‘Armed Antibodies’ are used in Philogen’s next-generation approach. Importantly, ‘Armed Antibodies’ may result in the improvement of the therapeutic index of medicinal agents which are already present on the market, or which have been investigated as non-targeted drugs and have failed because of insufficient selectivity.
Most preclinical and clinical activities of Philogen focus on the selective delivery of immunomodulatory moieties (e.g., cytokines) or cytotoxic payloads (e.g., drugs) to the site of disease.

SELECTED REFERENCES

Bootz and Neri (2016) Drug Discov. Today 21:180-9.
Pasche and Neri (2012) Drug Discov. Today 17:583-590;
Neri and Supuran (2011) Nat. Rev. Drug Discov. 10:767-77;
Roesli et al., (2011) J. Proteomics 74:539-46;
Fugmann et al., (2011) Kidney Int. 80:272-81;
Borgia et al., (2010) Cancer Res. 70:309-18;
Fugmann et al., (2010) Proteomics 10:2631-43;
Schliemann et al., (2010) Blood 115:736-44;
Villa et al. (2008) Int. J. Cancer 122:2405-13
Brack et al. (2006) Clin. Cancer Res. 12:3200-8;
Castronovo et al., (2006) Cell Proteomics 5:2083-91;
Neri and Bicknell (2005) Nat. Rev. Cancer 5:436-46;;
Rybak et al., (2005) Nat. Methods 2:291-8;
Viti et al. (1999) Cancer Res. 59:347-52;
Tarli et al. (1999) Blood 94:192-8;
Neri et al. (1997) Nature Biotech. 15:1271-5.