Tissue factor (TF) is aberrantly expressed in solid cancers and is thought to contribute to disease progression through its procoagulant activity and its capacity to induce intracellular signaling in complex with factor VIIa (FVIIa). Antibody-drug conjugates (ADCs), which combine the tumor-targeting capacity of monoclonal antibodies with the antitumor activity of cytotoxic agents, received renewed attention in recent years. BOC Sciences has over 10 years of expertise in bioconjugation and ADC development. Our ADC services offer the most comprehensive design and construction with the fastest turnaround times. We hope our ADC development services can help you accelerate your new drug discovery program.
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Tissue factor (TF), also called thromboplastin, factor III, or CD142, is aberrantly expressed in many solid cancers, including pancreatic, lung, cervical, prostate, bladder, ovarian, breast, and colon cancer. TF is the main physiologic initiator of the extrinsic coagulation pathway. Proteolytic cleavage of factor VII (FVII), the physiologic ligand of TF, generates activated FVII (FVIIa), which associates with TF to form the TF: FVIIa complex. This complex proteolytically activates coagulation factor X (FX) to generate FXa, eventually leading to thrombin generation and clot formation (Fig. 1). TF expression has been described on tumor cells and the tumor vasculature, and has been associated with poor disease prognosis and increased metastatic properties. In combination with the known internalizing capacity of TF, scientists explored the possibility of using tissue factor as a novel target for ADCs.
Fig. 1. Coagulation independent mechanisms of TF-mediated signaling (Mol. Pharmaceutics. 2015, 12(6): 2101-2111).
Tisotumab vedotin (Tivdak), is an antibody-drug conjugate or ADC targeting tissue factor (TF). An antibody targeting tissue factor (TF) is conjugated with effective microtubule disrupting agent monomethyl auristatin E (MMAE) through a cleavable linker, maleimidohexanoyl-pentyl-citrulline-p-amino benzyloxy carbonyl (mc-Val-cit-PABC). Currently, tisotumab vedotin is being jointly developed by Seattle Genetics and Genmab as a monotherapy or in combination with other therapies to treat recurrent and/or metastatic cervical cancer, ovarian cancer, and other solid tumors.
Cervical cancer is the fourth most common female cancer worldwide and results in over 300,000 deaths globally. The causative agent of cervical cancer is persistent infection with high-risk subtypes of the human papillomavirus and the E5, E6 and E7 viral oncoproteins cooperate with host factors to induce and maintain the malignant phenotype. Cervical cancer is a largely preventable disease and early-stage detection is associated with significantly improved survival rates. BOC Sciences is a service provider of ADC drug development. We offer comprehensive ADCs development services for the targeted cervical cancer treatment. Our unique target disovery and leading-edge bioconjugation programs can help clients obtain optimal ADC candidates.
Ovarian cancer, one of the deadliest gynaecological malignancies, is a global burden. In 2020, 313,959 new ovarian cancer cases and 207,252 deaths from ovarian cancer were reported, ranking eighth in both incidence and mortality among all types of cancers affecting women. The absence of cancer-specific symptoms and effective screening tools resulted in the diagnosis of ovarian cancer at an advanced stage with high disease recurrence and mortality rates. Histologically, the most common type of ovarian cancer is epithelial ovarian cancer (EOC), which accounts for >90% of all cases. The current standard treatment of EOC includes cytoreductive surgery (CRS) followed by taxane- and platinum-based chemotherapy. However, based on the successful development of TF-targeted ADC drug, ADCs have received extensive attention as a novel targeted therapy with great potential and prospects in the ovarian cancer treatment. As an experienced bioconjugate development company, our scientists utilize best-in-class proven conjugation systems to achieve your ADC development goals. We believe that our featured services will leverage our expertise and innovative technology platform to save time and cost on your project.
In addition to providing comprehensive ADC development services for cervical and ovarian cancer, BOC Sciences also provides target screening and antibody preparation modification services for other solid tumors, including prostate, bladder, esophagus, endometrial, lung, pancreatic, colorectal, head and neck cancers. We are building a platform of uniquely assembled, highly stable ADCs by leveraging proprietary conjugation, linker and payload technologies that enable us to utilize previously inaccessible targeting molecules and novel payloads to accelerate customers' ADC R&D track. Click here for more targeted ADC development services.
In ADC development for TF targets, BOC Sciences provides comprehensive services to assist in the design, development and optimization of ADCs for TF. Our services include target identification and validation, antibody selection and engineering, linker and payload selection, conjugation chemistry, ADC characterization, in vitro and in vivo evaluation and scale-up production.