Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels

Christian Fischer; Bart Jonckx; Massimiliano Mazzone; Serena Zacchigna; Sonja Loges; Lucia Pattarini; Emmanuel Chorianopoulos; Laurens Liesenborghs; Marta Koch; Maria De Mol; Monica Autiero; Sabine Wyns; Stephane Plaisance; Lieve Moons; Nico van Rooijen; Mauro Giacca; Jean-Marie Stassen; Mieke Dewerchin; Desire Collen; Peter Carmeliet

doi:10.1016/j.cell.2007.08.038

Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels

Christian Fischer, Bart Jonckx, Massimiliano Mazzone, Serena Zacchigna, Sonja Loges, Lucia Pattarini, Emmanuel Chorianopoulos, Laurens Liesenborghs, Marta Koch, Maria De Mol, Monica Autiero, Sabine Wyns, Stephane Plaisance, Lieve Moons, Nico van Rooijen, Mauro Giacca, Jean-Marie Stassen, Mieke Dewerchin, Desire Collen, Peter Carmeliet

Emerging Infectious Diseases

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Cell
Volume	131
Issue number	3
Pages (from-to)	463-75
Number of pages	13
ISSN	0092-8674
DOIs	https://doi.org/10.1016/j.cell.2007.08.038
Publication status	Published - 2-Nov-2007

Keywords

Animals
Antibodies, Monoclonal/adverse effects
Antineoplastic Agents/pharmacology
Blood Vessels/drug effects
Cell Line
Cell Movement/drug effects
Drug Resistance, Neoplasm/drug effects
Drug Screening Assays, Antitumor
Drug-Related Side Effects and Adverse Reactions
Health
Humans
Lymphangiogenesis/drug effects
Macrophages/cytology
Mice
Neoplasm Metastasis
Neoplasms/blood supply
Neovascularization, Pathologic/drug therapy
Placenta Growth Factor
Pregnancy Proteins/antagonists & inhibitors
Treatment Outcome
Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors

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10.1016/j.cell.2007.08.038

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Fischer, C., Jonckx, B., Mazzone, M., Zacchigna, S., Loges, S., Pattarini, L., Chorianopoulos, E., Liesenborghs, L., Koch, M., De Mol, M., Autiero, M., Wyns, S., Plaisance, S., Moons, L., van Rooijen, N., Giacca, M., Stassen, J.-M., Dewerchin, M., Collen, D., & Carmeliet, P. (2007). Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell, 131(3), 463-75. https://doi.org/10.1016/j.cell.2007.08.038

@article{cb3558d06da641558061ba7b5a5d4d1c,

title = "Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels",

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.",

keywords = "Animals, Antibodies, Monoclonal/adverse effects, Antineoplastic Agents/pharmacology, Blood Vessels/drug effects, Cell Line, Cell Movement/drug effects, Drug Resistance, Neoplasm/drug effects, Drug Screening Assays, Antitumor, Drug-Related Side Effects and Adverse Reactions, Health, Humans, Lymphangiogenesis/drug effects, Macrophages/cytology, Mice, Neoplasm Metastasis, Neoplasms/blood supply, Neovascularization, Pathologic/drug therapy, Placenta Growth Factor, Pregnancy Proteins/antagonists & inhibitors, Treatment Outcome, Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors",

author = "Christian Fischer and Bart Jonckx and Massimiliano Mazzone and Serena Zacchigna and Sonja Loges and Lucia Pattarini and Emmanuel Chorianopoulos and Laurens Liesenborghs and Marta Koch and {De Mol}, Maria and Monica Autiero and Sabine Wyns and Stephane Plaisance and Lieve Moons and {van Rooijen}, Nico and Mauro Giacca and Jean-Marie Stassen and Mieke Dewerchin and Desire Collen and Peter Carmeliet",

year = "2007",

month = nov,

day = "2",

doi = "10.1016/j.cell.2007.08.038",

language = "English",

volume = "131",

pages = "463--75",

journal = "Cell",

issn = "0092-8674",

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Fischer, C, Jonckx, B, Mazzone, M, Zacchigna, S, Loges, S, Pattarini, L, Chorianopoulos, E, Liesenborghs, L, Koch, M, De Mol, M, Autiero, M, Wyns, S, Plaisance, S, Moons, L, van Rooijen, N, Giacca, M, Stassen, J-M, Dewerchin, M, Collen, D & Carmeliet, P 2007, 'Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels', Cell, vol. 131, no. 3, pp. 463-75. https://doi.org/10.1016/j.cell.2007.08.038

TY - JOUR

T1 - Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels

AU - Fischer, Christian

AU - Jonckx, Bart

AU - Mazzone, Massimiliano

AU - Zacchigna, Serena

AU - Loges, Sonja

AU - Pattarini, Lucia

AU - Chorianopoulos, Emmanuel

AU - Liesenborghs, Laurens

AU - Koch, Marta

AU - De Mol, Maria

AU - Autiero, Monica

AU - Wyns, Sabine

AU - Plaisance, Stephane

AU - Moons, Lieve

AU - van Rooijen, Nico

AU - Giacca, Mauro

AU - Stassen, Jean-Marie

AU - Dewerchin, Mieke

AU - Collen, Desire

AU - Carmeliet, Peter

PY - 2007/11/2

Y1 - 2007/11/2

N2 - 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.

AB - 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.

KW - Animals

KW - Antibodies, Monoclonal/adverse effects

KW - Antineoplastic Agents/pharmacology

KW - Blood Vessels/drug effects

KW - Cell Line

KW - Cell Movement/drug effects

KW - Drug Resistance, Neoplasm/drug effects

KW - Drug Screening Assays, Antitumor

KW - Drug-Related Side Effects and Adverse Reactions

KW - Health

KW - Humans

KW - Lymphangiogenesis/drug effects

KW - Macrophages/cytology

KW - Mice

KW - Neoplasm Metastasis

KW - Neoplasms/blood supply

KW - Neovascularization, Pathologic/drug therapy

KW - Placenta Growth Factor

KW - Pregnancy Proteins/antagonists & inhibitors

KW - Treatment Outcome

KW - Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors

U2 - 10.1016/j.cell.2007.08.038

DO - 10.1016/j.cell.2007.08.038

M3 - Article

C2 - 17981115

SN - 0092-8674

VL - 131

SP - 463

EP - 475

JO - Cell

JF - Cell

IS - 3

ER -

Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels

Abstract

Keywords

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