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Veterinary PDGFRα/β Therapeutic Antibody Development
BioVenic provides veterinary PDGFRα/β therapeutic antibody development services with full-process coverage, supporting the development of PDGFRα/β therapeutic antibodies and facilitating research into their therapeutic potential for diseases in companion animals. PDGFRα and PDGFRβ exert essential functions in regulating cell proliferation and migration in companion animals, making them promising targets for diverse therapeutic approaches, particularly for tumor treatment.
Background of PDGFRα/β
| Full Name | Platelet derived growth factor receptor alpha/beta |
|---|---|
| Aliases | CD140A, PDGFR2, PDGFR-2, PDGFRA, PDGFRα/ CD140B, IBGC4, IMF1, JTK12, KOGS, PDGFR1, PDGFR-1, PDGFRB, PDGFRβ, PENTT. |
| Target Profile | As tyrosine kinase receptors on the cell surface, PDGFRα and PDGFRβ become parts of the cytokine receptor superfamily. They are activated by binding ligands from PDGF family and play roles in proliferation, migration, differentiation, and survival processes in various cell types such as endothelial cells, fibroblasts, and vascular smooth muscle cells. Abnormal expression and activation of PDGFR are also associated with the growth, development, and microenvironment regulation of tumors. |
MoA of PDGFRα/β
Both PDGFRα and PDGFRβ are involved in several well-characterized signaling pathways, such as Ras/MAPK, PI3K, and PLC-γ. PDGFR primarily connects to the Ras/MAPK pathway through adaptor proteins Grb2 and Shc. Grb2 binds to the activated PDGFR via its SH2 domain and complexes with Sos1 via its SH3 domain. Sos1, in turn, activates Ras, leading to downstream activation of Raf-1 and the MAPK cascade. MAPK signaling activates gene transcription, stimulating cell growth, differentiation, and migration. PDGFR also activates the PI3K pathway, promoting actin reorganization, directed cell movement, stimulation of cell growth, and inhibition of apoptosis. PLC-γ binds to PDGFR, leading to intracellular calcium mobilization and PKC activation through phosphorylation, stimulating cell growth and movement. PDGFR also interacts with integrins, enhancing cell proliferation, migration, and survival.
Fig.1 Simplified depiction of receptor interactions: PDGFR-α and PDGFR-β crosstalk with cadherin-11, and β-catenin's interaction with ERK through DUSP1 inhibitor. 1,2
Application in Veterinary Therapeutics
Overexpression of PDGFRα/β has been studied in various companion animal tumors, including canine mast cell tumors, astrocytomas, lymphomas, osteosarcomas, sac adenocarcinomas, thyroid carcinomas, hemangiosarcomas, cutaneous peripheral nerve sheath tumors, and mammary tumors. This highlights the importance of PDGFRα/β in animal tumor biology, as its role in angiogenesis, promoting cancer development, and potential invasiveness. Inhibition of PDGFR has also shown significant therapeutic effects in feline injection site sarcomas, and PDGFRβ expression is found in most feline histiocytic diseases. Therefore, considering the use of PDGFRα/β therapeutic antibodies for inhibiting PDGFRα/β could have desired therapeutic effects in various canine and feline tumors as well as other related diseases.
Veterinary PDGFRα/β Therapeutic Antibody Development Services
PDGFRα/β is involved in companion animal tumor cell differentiation, invasion, and angiogenesis, making them the target for therapeutic antibody development for treatment. BioVenic has established a platform for the development of veterinary PDGFRα/β therapeutic antibodies. Leveraging extensive antibody preparation experience, we use hybridoma, single B cell, and phage display techniques for the development of high-quality veterinary PDGFRα/β therapeutic antibodies. Additionally, we offer antibody characterization and engineering services, aiming to develop high-affinity and low-immunogenicity antibodies.
Please click the link below for more information about our veterinary PDGFRα/β therapeutic antibody development services.
Fig.2 Antibody discovery and production methods: from mouse hybridoma to transgenic mice. (BioVenic Original)
Why Choose Us?
Our one-stop veterinary therapeutic antibody development service covers the entire process, from animal immunization to antibody preparation, screening, and late-stage characterization and validation.
Our antibody engineering services include antibody caninization/felinization, affinity maturation, and Fc engineering, reducing immunogenicity for specific species, enhancing affinity, and extending the half-life of antibodies.
We provide species-specific antibody development services to improve compatibility and efficacy within specific species and reduce safety issues related to immunogenicity.
Frequently Asked Questions
What core downstream signaling cascades are triggered by activated PDGFRα and PDGFRβ receptors?
After binding PDGF ligands, phosphorylated PDGFRα/β activate three major functional pathways: Ras/MAPK for cell proliferation, PI3K/AKT to suppress apoptosis and boost cell migration, and PLC-γ which mediates calcium influx and PKC activation. The receptors also crosstalk with cadherin-11 and β-catenin to regulate tumor cycle protein Cyclin-D1 expression.
What broad spectrum of canine and feline tumors are driven by overactivated PDGFRα/β signaling?
In dogs: mast cell tumor, osteosarcoma, hemangiosarcoma, mammary carcinoma, astrocytoma and nerve sheath tumor. In cats: injection site sarcoma and histiocytic disorders. Overexpression of PDGFR receptors drives tumor angiogenesis, cell invasion and lesion progression across these malignancies.
What dual anti-tumor effects do PDGFRα/β neutralizing antibodies achieve for companion animal tumor research?
Antibodies block ligand-receptor binding to shut down proliferative signaling, directly inhibiting tumor cell growth and migration. Meanwhile, they suppress PDGFR-mediated vascular endothelial activation to cut tumor angiogenesis, reducing nutrient supply to malignant lesions and restraining metastasis potential.
What distinct crosstalk mechanism exists between PDGFR signaling and cadherin/β-catenin pathways?
Cadherin-11 negatively modulates both PDGFRα and PDGFRβ activity. Activated PDGFR signaling elevates ERK levels, while DUSP1 acts as a suppressor to limit ERK accumulation. ERK further interacts with β-catenin to control Cyclin-D1 transcription, which determines tumor cell cycle progression speed.
What customized antibody optimization can we deliver to improve in vivo performance for canine and feline research?
We provide multi-dimensional engineering: caninization/felinization to cut heterologous immunogenicity, affinity maturation to strengthen target binding, and Fc region modification to extend blood circulation half-life, supporting long-term tumor intervention experiments in companion animal models.
Partner with BioVenic
Therapeutics targeting PDGFRα/β have the potential to be developed for inhibiting the growth and angiogenesis of various companion animal tumors and treating certain fibrotic diseases. BioVenic offers veterinary PDGFRα/β therapeutic antibody development services. Our services cover the entire development process, meeting your needs at each development stage. If you require development of veterinary PDGFRα/β therapeutic antibodies, please contact us immediately.
References
- Karagöz, Zeynep, et al. "Computational evidence for multi-layer crosstalk between the cadherin-11 and PDGFR pathways." Scientific Reports 13.1 (2023): 15804.
- Image retrieved from Figure 1 "The schematic representation of receptor level crosstalk between growth factor receptors (PDGFR-α and PDGFR-β) and cadherin-11, and the proposed crosstalk between β-catenin and ERK via the ERK inhibitor DUSP1." Karagöz, Zeynep, et al., 2023, used under [CC BY 4.0], the image title was changed to "Simplified depiction of receptor interactions: PDGFR-α and PDGFR-β crosstalk with cadherin-11, and β-catenin's interaction with ERK through DUSP1 inhibitor."
