Specific Antibody Fragment Ligand Traps Blocking FGF1 Activity

Area of Science:

• Molecular Biology
• Cancer Research
• Immunology

Background:

• Fibroblast Growth Factor 1 (FGF1) and its receptors (FGFRs) are critical for cell growth and differentiation.
• Dysregulated FGFR signaling drives tumor progression and angiogenesis in cancers like lung and breast cancer.
• Targeting FGF1 offers a potential therapeutic strategy for FGF1-driven malignancies.

Purpose of the Study:

• To identify and characterize novel antibody fragments that selectively bind FGF1.
• To evaluate the ability of these antibodies to inhibit FGF1-FGFR interactions and downstream signaling.
• To assess the therapeutic potential of FGF1-targeting antibodies in cancer treatment.

Main Methods:

• Phage display selection was employed to isolate FGF1-specific single-chain variable fragment (scFv) antibodies.
• Selected scFvs were expressed, characterized for FGF1 binding affinity, and assessed for inhibition of FGF1-induced signaling.
• scFvs were engineered into scFv-Fc fusion proteins to enhance affinity and therapeutic applicability.

Main Results:

• Three scFv clones with selective binding to FGF1 were identified.
• scFv-Fc fusion proteins demonstrated significantly increased affinity for FGF1 compared to scFvs.
• Both scFvs and scFv-Fc formats exhibited potent antiproliferative activity in vitro cancer models.

Conclusions:

• Novel antibody fragments targeting FGF1 were successfully developed.
• These antibodies effectively inhibit FGF1 binding and signaling, leading to reduced cancer cell proliferation.
• The characterized FGF1 inhibitors represent promising tools for developing targeted cancer therapies.