ADC Development Services Targeting TF

Antibody-drug conjugates (ADCs) possess advantages including tumor-targeting capacity of monoclonal antibodies and the antitumor activity of cytotoxic agents, which have been considered as one of the most promising therapeutic approaches for cancer treatment. Creative Biolabs has over 10 years of expertise in the antibody production and bio-conjugation field. Our ADCs service provides the most comprehensive design and construction along with the fastest turnaround time. We hope our ADC development services can help you accelerate your novel drug discovery project.

Introduction of TF

Tissue factor (TF), also known as CD142 thromboplastin or factor III, is encoded by the F3 gene. It belongs to the cytokine receptor protein superfamily and is expressed in subendothelial tissue and leukocytes. It also exists in various organs such as the brain, heart, intestine, kidney, lung, placenta, uterus, and testes. During an abnormal expression, it is highly expressed in many solid cancers, including pancreatic, lung, cervical, prostate, bladder, ovarian, breast, and colon cancer. TF contains three domains, an extracellular domain, a transmembrane domain and a cytosolic domain. As a main physiologic initiator of the extrinsic coagulation pathway, TF interacts with factor VII (FVII) to generate TF:FVIIa complex leading to thrombin generation and clot formation. In addition, TF: FVIIa complex also can induce an intracellular signaling cascade by activation of protease-activated receptor 2 (PAR-2) to produce the proangiogenic factors, cytokines and adhesion molecules.

Fig.1 Cellular sources of tissue factor (TF) that trigger thrombosis and disseminated intravascular coagulation. (Grover, 2018)

Anti-TF ADC in Cervical Cancer

TF presents significant internalization capacity, which is regarded as a novel target for ADCs development. Tisotumab vedotin (also known as HuMax‑TF‑ADC) is an ADC targeting the TF, composed of a Genmab's human monoclonal antibody (mAb) conjugated to the cytotoxic drug monomethyl auristatin E (MMAE) through a protease-cleavable linker. Preclinical trial results demonstrated that Tisotumab vedotin has potent cytotoxicity in vitro and in vivo. Besides, this ADC showed significant antitumor activity and complete tumor regression in patient-derived xenograft (PDX) models. In addition, clinical studies showed that Tisotumab vedotin has good response rate and tolerable safety profile. Thus, the ADC is a promising novel antitumor agent for the cervical cancer treatment.

Fig.2 Tisotumab vedotin mechanism of action. (Vergote, 2017)

What Can We Do for You?

As one of the best partners for scientists in the process of ADCs discovery and development, Creative Biolabs provides a wide range of ADCs construction services against different targets. As an experienced antibody-related drug discovery company, our scientists utilize first-class and mature conjugation system to achieve your goal of ADCs development. We believe our featured services will save the time and cost of your programs by taking advantage of our expertise and innovative technology platforms. 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 right now.

References

1. Grover, S. P.; Mackman, N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arteriosclerosis, thrombosis, and vascular biology. 2018, 38(4): 709-725.
2. Vergote, I.; et al. A phase IIa study of tisotumab vedotin (HuMax-TF-ADC) in patients with relapsed, recurrent and/or metastatic cervical cancer. Annals of Oncology. 2017, 28: 331.

For Research Use Only. NOT FOR CLINICAL USE.