Related Experiment Video
Updated: Nov 30, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Novel FGFR4-Targeting Single-Domain Antibodies for Multiple Targeted Therapies against Rhabdomyosarcoma
Nagjie Alijaj1,2,3, Sandrine Moutel4,5, Zelia L Gouveia4,6
1Department of Oncology, Children's Research Center, University Children's Hospital Zurich, 8032 Zurich, Switzerland.
Abstract:
The fibroblast growth factor receptor 4 (FGFR4) is overexpressed in rhabdomyosarcoma (RMS) and represents a promising target for treatments based on specific and efficient antibodies. Despite progress, there is an urgent need for targeted treatment options to improve survival rates, and to limit long-term side effects. From phage display libraries we selected FGFR4-specific single-domain antibodies (sdAb) binding to recombinant FGFR4 and validated them by flow cytometry, surface plasmon resonance, and fluorescence microscopy. The specificity of the selected sdAb was verified on FGFR4-wild type and FGFR4-knock out cells. FGFR4-sdAb were used to decorate vincristine-loaded liposomes and to generate chimeric antigen receptor (CAR) T cells. First, incubation of RMS cells with FGFR4-sdAb revealed that FGFR4-sdAb can block FGF19-FGFR4 signaling via the MAPK pathway and could therefore serve as therapeutics for FGFR4-dependent cancers. Second, FGFR4-targeted vincristine-loaded liposomes bound specifically to RMS cells and were internalized by the receptor, demonstrating the potential for active drug delivery to the tumor. Third, FGFR4-CAR T cells, generated with one sdAb candidate, demonstrated strong and specific cytotoxicity against FGFR4 expressing RMS cells. We selected novel FGFR4-sdAb with high specificity and nano- to picomolar affinities for FGFR4 which have the potential to enable multiple FGFR4-targeted cancer therapy approaches.
Insights
Novel single-domain antibodies targeting fibroblast growth factor receptor 4 (FGFR4) show promise for treating rhabdomyosarcoma. These antibodies enable targeted drug delivery and CAR T-cell therapies, potentially improving outcomes for FGFR4-dependent cancers.
Area of Science:
- Oncology
- Immunotherapy
- Drug Delivery
Background:
- Fibroblast growth factor receptor 4 (FGFR4) is overexpressed in rhabdomyosarcoma (RMS), presenting a therapeutic target.
- Current treatments for RMS have limitations, necessitating novel targeted approaches to improve survival and reduce side effects.
Purpose of the Study:
- To develop and validate novel single-domain antibodies (sdAbs) targeting FGFR4 for potential cancer therapies.
- To explore the therapeutic potential of FGFR4-targeting sdAbs in drug delivery systems and chimeric antigen receptor (CAR) T-cell therapy.
Main Methods:
- Selection of FGFR4-specific sdAbs using phage display.
- Validation of sdAb binding affinity and specificity using flow cytometry, surface plasmon resonance, and microscopy.
- Application of sdAbs in FGFR4-blocking assays, targeted liposome drug delivery, and CAR T-cell generation.
Main Results:
- Novel FGFR4-specific sdAbs with high affinity (nano- to picomolar) were identified.
- FGFR4-sdAbs demonstrated the ability to block FGF19-FGFR4 signaling via the MAPK pathway.
- FGFR4-targeted liposomes were effectively internalized by RMS cells, and FGFR4-CAR T cells exhibited specific cytotoxicity against RMS cells.
Conclusions:
- The developed FGFR4-sdAbs are highly specific and possess strong binding affinities, making them suitable for multiple cancer therapy strategies.
- These sdAbs offer potential for targeted treatment of FGFR4-dependent cancers, including RMS, through direct therapeutic effects, enhanced drug delivery, and immunotherapy.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...