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Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels
Authors:Fischer Christian  Jonckx Bart  Mazzone Massimiliano  Zacchigna Serena  Loges Sonja  Pattarini Lucia  Chorianopoulos Emmanuel  Liesenborghs Laurens  Koch Marta  De Mol Maria  Autiero Monica  Wyns Sabine  Plaisance Stephane  Moons Lieve  van Rooijen Nico  Giacca Mauro  Stassen Jean-Marie  Dewerchin Mieke  Collen Desire  Carmeliet Peter
Affiliation:Department for Transgene Technology and Gene Therapy, VIB, 3000, Leuven, Belgium.
Abstract:Novel antiangiogenic strategies with complementary mechanisms are needed to maximize efficacy and minimize resistance to current angiogenesis inhibitors. We explored the therapeutic potential and mechanisms of alphaPlGF, an antibody against placental growth factor (PlGF), a VEGF homolog, which regulates the angiogenic switch in disease, but not in health. alphaPlGF inhibited growth and metastasis of various tumors, including those resistant to VEGF(R) inhibitors (VEGF(R)Is), and enhanced the efficacy of chemotherapy and VEGF(R)Is. alphaPlGF inhibited angiogenesis, lymphangiogenesis, and tumor cell motility. Distinct from VEGF(R)Is, alphaPlGF prevented infiltration of angiogenic macrophages and severe tumor hypoxia, and thus, did not switch on the angiogenic rescue program responsible for resistance to VEGF(R)Is. Moreover, it did not cause or enhance VEGF(R)I-related side effects. The efficacy and safety of alphaPlGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alphaPlGF may constitute a novel approach for cancer treatment.
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