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Updated: Dec 31, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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A Novel Antitumor Strategy: Simultaneously Inhibiting Angiogenesis and Complement by Targeting VEGFA/PIGF and C3b/C4b

Huiling Wang1, Yiming Li1,2, Gang Shi1

  • 1State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Molecular Therapy Oncolytics
|January 8, 2020
PubMed

Insights

This study introduces a novel combination therapy blocking vascular endothelial growth factor (VEGF) and complement, showing synergistic antitumor effects against resistant cancers. This dual blockade effectively inhibits tumor growth and promotes cancer cell death.

Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Vascular Endothelial Growth Factor (VEGF) antibodies are crucial for tumor therapy but face limitations due to drug resistance and alternative angiogenic pathways.
  • Complement proteins play a role in cancer progression and angiogenesis, presenting a potential target for cancer therapy.
  • The combined therapeutic potential of simultaneously blocking VEGF and complement in cancer treatment remains unexplored.

Purpose of the Study:

  • To investigate the synergistic antitumor effects of combined VEGF and complement blockade.
  • To evaluate the efficacy of novel fusion proteins targeting VEGFA/PIGF and C3b/C4b.
  • To elucidate the mechanisms underlying the combination therapy's anti-tumor activity.

Main Methods:

  • Generation of a humanized soluble VEGFR-Fc fusion protein (VID) and a CR1-Fc fusion protein (CID).
  • In vitro assessment of VID and CID bioactivities, including inhibition of VEGF-induced angiogenesis and complement-induced hemolysis.
  • In vivo evaluation of combination therapy in colitis-associated colorectal cancer (CAC) and orthotopic 4T1 breast cancer models.

Main Results:

  • VID and CID demonstrated high affinity for their respective ligands and potent bioactivities in vitro.
  • Combined VID and CID therapy exhibited synergistic antitumor effects in both CAC and 4T1 breast cancer models.
  • Combination therapy suppressed tumor angiogenesis, proliferation, and myeloid-derived suppressor cell (MDSC) infiltration while enhancing tumor cell apoptosis.

Conclusions:

  • Simultaneous blockade of VEGF and complement presents a promising therapeutic strategy for overcoming anti-VEGF resistance in tumors.
  • This dual blockade offers a novel approach for treating chronic inflammation-associated and resistant cancers.
  • The combination therapy effectively targets multiple tumor-promoting mechanisms within the tumor microenvironment.
Keywords:
CR1-Fc fusion proteinMDSCsVEGFR-Fc fusion proteinangiogenesiscombination therapy

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