Characterization of therapeutic antibodies targeting lymphatic and vascular resistance factor for the treatment of hypervascularized and highly metastatic cancers.
- 1Kekkan Biologics, Strasbourg, France.
- 2University Côte d'Azur, Institute for Research on Cancer and Aging of Nice (IRCAN) UMR CNRS 7284/U INSERM 1081, France.
- 3University Côte d'Azur, Institute for Research on Cancer and Aging of Nice (IRCAN) UMR CNRS 7284/U INSERM 1081, 3D-Hub-S platform, France.
Abstract
Angiogenesis is a major driver of tumor progression and a validated therapeutic target in highly vascularized cancers such as clear cell renal cell carcinoma. However, the clinical benefit of antivascular endothelial growth factor therapies is limited by the emergence of resistance. We identified a vascular endothelial growth factor A splice variant, termed Lymphatic and Vascular Resistance Factor (LVRF), which promotes both angiogenesis and lymphangiogenesis and is upregulated following anti-angiogenic treatment. To therapeutically target this pathway, we generated fully human monoclonal antibodies against LVRF. Lead antibodies displayed high specificity and nanomolar affinity and effectively inhibited LVRF-driven biological activities. Anti-LVRF antibodies reduced renal carcinoma cell invasion, inhibited vascular and lymphatic endothelial responses, and suppressed lymphatic endothelial cell sprouting. In vivo, treatment significantly reduced the growth of bevacizumab-resistant renal carcinoma xenografts, induced regression of blood and lymphatic vessels, and decreased metastatic dissemination in zebrafish models. These findings identify LVRF as a mediator of resistance to anti-angiogenic therapy and support therapeutic targeting of LVRF as a novel strategy for vascularized tumors resistant to current antivascular endothelial growth factor treatments.
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BibTeX
@article{david2026characterization,
title = {{Characterization of therapeutic antibodies targeting lymphatic and vascular resistance factor for the treatment of hypervascularized and highly metastatic cancers.}},
author = {Marion David and Arthur Karaulic and Audrey Bennetot and Clémence Fournier and Quentin Odet and Arthur Gouraud and Isabelle Bourget and Cédric Gaggioli and Sandy Giuliano and Frédéric Luciano and Olivier Léger and Zaki Sellam and Gilles Pagès},
journal = {Molecular oncology},
year = {2026},
month = oct,
doi = {10.1002/1878-0261.70343},
url = {https://europepmc.org/article/MED/42900503},
note = {CC BY},
}
RIS
TY - JOUR
TI - Characterization of therapeutic antibodies targeting lymphatic and vascular resistance factor for the treatment of hypervascularized and highly metastatic cancers.
AU - Marion David
AU - Arthur Karaulic
AU - Audrey Bennetot
AU - Clémence Fournier
AU - Quentin Odet
AU - Arthur Gouraud
AU - Isabelle Bourget
AU - Cédric Gaggioli
AU - Sandy Giuliano
AU - Frédéric Luciano
AU - Olivier Léger
AU - Zaki Sellam
AU - Gilles Pagès
PY - 2026
DA - 2026/10/20
JO - Molecular oncology
DO - 10.1002/1878-0261.70343
UR - https://europepmc.org/article/MED/42900503
AB - Angiogenesis is a major driver of tumor progression and a validated therapeutic target in highly vascularized cancers such as clear cell renal cell carcinoma. However, the clinical benefit of antivascular endothelial growth factor therapies is limited by the emergence of resistance. We identified a vascular endothelial growth factor A splice variant, termed Lymphatic and Vascular Resistance Factor (LVRF), which promotes both angiogenesis and lymphangiogenesis and is upregulated following anti-angiogenic treatment. To therapeutically target this pathway, we generated fully human monoclonal antibodies against LVRF. Lead antibodies displayed high specificity and nanomolar affinity and effectively inhibited LVRF-driven biological activities. Anti-LVRF antibodies reduced renal carcinoma cell invasion, inhibited vascular and lymphatic endothelial responses, and suppressed lymphatic endothelial cell sprouting. In vivo, treatment significantly reduced the growth of bevacizumab-resistant renal carcinoma xenografts, induced regression of blood and lymphatic vessels, and decreased metastatic dissemination in zebrafish models. These findings identify LVRF as a mediator of resistance to anti-angiogenic therapy and support therapeutic targeting of LVRF as a novel strategy for vascularized tumors resistant to current antivascular endothelial growth factor treatments.
SN - 1574-7891
SN - 1878-0261
ER -