ADC Development Services Targeting 5T4

Antibody-drug conjugate (ADC) has been proven to be an imperative therapeutic agent in cancer treatment. In recent years, several ADCs have been developed as effective bio-drugs, and many other ADCs are developed and investigated in different clinical trial stages.

Creative Biolabs is an expert in the field of antibody development and antibody-drug conjugation. During the past decade, we have developed a handful of reagents of various functional groups for ADCs construction. At present, we provide a full range of ADCs development services against the 5T4 biomarker. We believe our featured services and products will facilitate your novel drug discovery project.

Introduction of 5T4

5T4, also known as trophoblast glycoprotein, is a transmembrane molecule encoded by the TPBG gene. It has a cytoplasmic domain, a transmembrane region and an N-glycosylated extracellular domain containing multiple leucine-rich repeat regions. 5T4 is often called oncofetal antigen, because it also exists in foetal trophoblast or trophoblast glycoprotein (TPBG). It plays a crucial role in regulating the epithelial-mesenchymal transition, cytoskeletal organization, and motility through the Wnt signaling. What’s more, 5T4 is highly expressed in a number of solid tumors including lung, breast, ovarian, endometrial, bladder, pancreatic, esophageal, and gastric cancers. Thus, it is considered as a potential marker in targeted cancer immunotherapy.

Fig.1 Crystal Structure of the Human 5T4/WAIF1Ecto. (Zhao, 2014)

Anti-5T4 ADC in Solid Tumors

PF-06263507 (also known as ADC 5T4) is an ADC specifically targeting 5T4, which consists of a humanized anti-5T4 IgG1 antibody PF-06281192 (huA1 mAb) linked to the microtubule-disrupting agent monomethyl auristatin F (MMAF) through a maleimidocaproyl (mc) linker. PF-06263507 was designed for the treatment of adult patients with 5T4-positive advanced solid tumors. In preclinical trials, PF-06263507 displayed specific binding to 5T4-positive tumor cells and rapid internalization. In addition, compared with the unconjugated antibody (PF-06281192) or a control ADC, PF-06263507 showed more potent anti-tumor activity against several human tumor xenografts with 5T4 expression. Importantly, clinical trials demonstrated that the ADC possesses significant antitumor activity in patients with advanced solid malignancies with acceptable safety, tolerability, and pharmacokinetics (PK).

Fig.2 Structure of PF-06263507 (ADC 5T4). (Shapiro, 2017)

What Can We Do for You?

Creative Biolabs provides a complete portfolio of ADCs services including monoclonal antibody production, drug or linker-payload synthesis, and bio-conjugation. As a leading service provider in custom ADCs development, Creative Biolabs offers a wide range of industry-leading platforms for ADCs construction targeting tumor-associated antigen, such as the 5T4. We can customize a discovery and development path to fit your exact needs. Our scientists will work with you to generate custom antibodies and drugs for your new ADCs drug development programs. For more information, please contact us.

Our ADCs development services include but not limited to:

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

References

1. Zhao, Y.; et al. Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1. Structure. 2014, 22(4): 612-620.
2. Shapiro, G. I.; et al. First-in-human trial of an anti-5T4 antibody-monomethyl auristatin conjugate, PF-06263507, in patients with advanced solid tumors. Investigational new drugs. 2017, 35(3): 315-323.

For Research Use Only. NOT FOR CLINICAL USE.