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Published on: September 1, 2016
Effect of Ang-2-VEGF-A Bispecific Antibody in Renal Cell Carcinoma
Hideharu Bessho1,2,3, Bernice Wong1,2, Dachuan Huang1,2
1a Laboratory of Cancer Epigenome , National Cancer Centre Singapore , Singapore.
Abstract:
The blockade of VEGF pathway has been clinically validated as an initial treatment for renal cell carcinoma (RCC). Angiopoietin-2 (Ang-2) has been indicated as a key regulator for angiogenesis escape. The effect of a novel bispecific antibody (A2V CrossMab) against both Ang-2 and VEGF was investigated in comparison with either factor. A2V CrossMab significantly reduced tumor volume, vessel density, and interstitial fluid pressure compared to either monotherapy of anti-VEGF or anti-Ang-2. Host-derived angiogenesis-related genes have been significantly down-regulated in A2V CrossMab group. These data demonstrate that A2V CrossMab has additive anti-tumor effect for the treatment of RCC.
Insights
A novel bispecific antibody targeting Angiopoietin-2 (Ang-2) and VEGF shows enhanced anti-tumor effects in renal cell carcinoma (RCC) models. This A2V CrossMab therapy significantly reduced tumor growth and improved outcomes compared to single-target treatments.
Area of Science:
- Oncology
- Immunology
- Vascular Biology
Background:
- Vascular Endothelial Growth Factor (VEGF) pathway blockade is a validated treatment for renal cell carcinoma (RCC).
- Angiopoietin-2 (Ang-2) plays a critical role in escaping anti-angiogenic therapy.
- Dual targeting may overcome resistance mechanisms in RCC treatment.
Purpose of the Study:
- To evaluate the efficacy of a novel bispecific antibody (A2V CrossMab) targeting both Ang-2 and VEGF.
- To compare the anti-tumor effects of A2V CrossMab with monotherapies targeting either Ang-2 or VEGF in RCC.
- To investigate the impact of A2V CrossMab on tumor angiogenesis and related gene expression.
Main Methods:
- In vivo studies using RCC models to assess tumor growth and vascularization.
- Administration of A2V CrossMab, anti-VEGF monotherapy, and anti-Ang-2 monotherapy.
- Measurement of tumor volume, vessel density, interstitial fluid pressure, and angiogenesis-related gene expression.
Main Results:
- A2V CrossMab significantly reduced tumor volume, vessel density, and interstitial fluid pressure compared to monotherapies.
- Host-derived angiogenesis-related genes were significantly down-regulated in the A2V CrossMab treatment group.
- The bispecific antibody demonstrated additive anti-tumor effects.
Conclusions:
- A2V CrossMab exhibits superior anti-tumor efficacy in RCC models compared to targeting Ang-2 or VEGF alone.
- Dual inhibition of Ang-2 and VEGF pathways represents a promising therapeutic strategy for renal cell carcinoma.
- This approach may enhance treatment outcomes by overcoming angiogenesis escape mechanisms.
