Decorin: A Growth Factor Antagonist for Tumor Growth Inhibition

Figure 3

Schematic representation of the mechanism of action of the multifunctional therapeutic molecule CAR-decorin. CAR-decorin ① is a systemically administered, target-seeking, multifunctional biotherapeutic that inhibits numerous growth factors involved in tumor growth and progression. The molecule can be targeted to the angiogenic vasculature, whether it is induced by injury or by rapid cancer growth, taking place at any organ of the body ② (or multiple organs, i.e., metastases, simultaneously). The CAR homing peptide targets angiogenic vasculature ② and as it is a potent cell and tissue penetrating peptide, it can penetrate deep into target organ ③. Thus, the peptide (and any payload attached to it) then extravasates into surrounding tissue ③, where it binds to its receptor(s) on the cell surface of the target cells ③. CAR binding to heparan sulfate proteoglycans provides docking sites in the proximity of such growth factors as TGF-β1 and TGF-β2 ④, facilitating the neutralization of these growth factors by the therapeutic part of the molecule, decorin ④. This mechanism results in a therapeutic response. Picture by Helena Schmidt; reproduced with permission from Finnish Medical Journal Duodecim (originally published in [96]).