ADC Development Services Targeting FGFR3

Antibody-drug conjugates (ADC) have emerged as one of the most promising new tools for the specific ablation of tumor cells currently. Several ADCs have been approved to use in cancer treatment and a variety of ADCs are in different phases of clinical development.

Creative Biolabs, a leading biotechology service supplier, focuses on novel therapeutics discovery and drug development. Relying on our state-of-the-art technology platform and rich experience, we provide one-stop ADCs development services targeting FGFR3 to help clients boost their projects. From synthetic route design and optimization, to complex conjugates production and characterization, we strive with excellence and confidence to offer high quality and cost-effective ADCs services for our clients.

Introduction of FGFR3

Fibroblast growth factor receptor 3 (FGFR3), also known as CD333, is a tyrosine-protein kinase encoded by the FGFR3 gene located on chromosome 4, location p16.3 in humans. It contains an extracellular region, three immunoglobulin-like domains, a single hydrophobic transmembrane region and a cytoplasmic tyrosine kinase domain. It is widely expressed in tissues such as the cartilage, brain, intestine, and kidneys. FGFR3 acts as cell-surface receptor for fibroblast growth factors involved in the regulation of cell proliferation, differentiation and apoptosis. It is a negative regulator of endochondral bone growth playing a critical role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is essential for normal skeleton development. Besides, FGFR3 can also promote cancer cell proliferation. It is highly expressed on tumor cells including bladder cancer, multiple myeloma, non-small cell lung cancer (NSCLC), glioblastoma multiforme, and cervical cancer. Thus, FGFR3 serves as a promising biomarker in the therapy of cancer.

Fig.1 Molecular aberrations leading to FGFR pathway activation. (Chae, 2017)

Anti-FGFR3 ADC in Metastatic Cancers

The overexpression of FGFR3 on metastatic cancer cells makes it as a potential target in ADC therapy. One example, LY3076226, is a novel ADC targeting the FGFR3, which is composed of a fully human anti-FGFR3 antibody, IMC-D11, linked to a cytotoxic payload, the maytansine-derivative DM4 through a cleavable linker (sulfo-SPDB). Preclinical trials demonstrated that LY3076226 can bind to the human FGFR3 protein with high affinity, and internalize to carry the potent cytotoxic drug into tumor cells causing cell cycle arrest and cell death. LY3076226 significantly inhibited tumor growth in several PDX models with a durable complete response. Besides, LY3076226 showed superior efficacy compared to the naked IMC-D11 Ab. Currently, the ADC is investigated in the clinical phase I for the treatment of advanced metastatic cancers.

Fig.2 Structure of LY3076226. (Elkins, 2012)

What Can We Do for You?

Creative Biolabs offers one-stop integrated ADCs development services including the development of antibodies, linkers, and cytotoxins to the production of effective ADC. Additionally, we apply innovative linker technologies to ensure that payload conjugate to the antibodies effectively and that the drugs are only released into the target cells. With more than ten years of experience, we are fully confident that our first-class service can significantly facilitate your ADC drug development process.

Our ADCs development services including:

• ADC Antibody Screening
• DrugLnk™ Custom Synthesis
• Antibody Design and Conjugation
• ADC in vitro Analysis
• ADC in vivo Analysis

For more information, please contact us.

References

1. Chae, Y. K.; et al. Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application. Oncotarget. 2017, 8(9): 16052.
2. Elkins, K.; et al. FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma. Molecular cancer therapeutics. 2012, 11(10): 2222-2232.

For Research Use Only. NOT FOR CLINICAL USE.