ADC Development Services Targeting TROP2

A growing body of evidence suggests that TROP2 is a promising molecular target for the treatment of various malignancies. As novel targeted therapy with great potential, antibody-drug conjugates (ADCs) targeting a specific antigen inherit superiorities of antibody with the drug module, and more remarkably, expand the therapeutic window. Creative Biolabs is a leading provider of ADC services and is well placed to see the challenges and issues in developing an effective ADC. With deep understanding of the each procedure in ADC development, Creative Biolabs is fully prepared to provide customized ADC development service targeting TROP2 for our worldwide customers.

Introduction of TROP2

TROP2, also known as tumor-associated calcium signal transducer 2 (TACSTD2), is a 35 kD, 323 amino acid, type I transmembrane glycoprotein. TROP2 contains a large extracellular (EC) domain, a single transmembrane (TM) domain, and a short intracellular tail (IC). TROP2 is over-expressed in the majority of human epithelial cancers, including human colorectal, pancreatic, lung, oesophageal, oral, breast, uterine, glioma, and ovarian cancers and thus TROP2 has become an attractive immunotherapeutic target in various cancer treatment.

Fig.1 Domain organization of TROP2. (Pavšič, 2015)

Anti-TROP2 ADC in NSCLC, SCLC, Breast Cancer, Ovarian Cancer, Urothelial Tumors

TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells. Emerging evidence suggests that TROP2-targeting therapies are efficacious and safe in patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). TROP2 thus has been used as a ADC target of lung cancer therapy.

Several ongoing clinical trials for TROP2-targeting therapies are showing signs of efficacy. Taking the Sacituzumab govitecan (IMMU-132) as an example, it is an ADC targeting TROP2. This ADC is composed of a humanized anti-TROP2 antibody conjugated with a toxic payload SN-38. IMMU-132 can deliver markedly higher levels of SN-38 to tumors, with an improved therapeutic index. The Phase I clinical study with IMMU-132 was designed as a basket trial including patients with diverse metastatic epithelial cancers who had failed conventional treatments, with 10 indications studied initially (i.e., colorectal cancer, gastric cancer, hepatocellular cancer, NSCLC, SCLC, ovarian cancer, pancreatic cancer, prostate cancer, triple-negative breast cancer, and urothelial cancer). The expanded Phase II clinical experience with IMMU-132 in patients given 10 mg/kg as their starting dose has been reported for NSCLC, SCLC, triple-negative breast cancer, ovarian cancer and urothelial cancer. Summarizing, IMMU-132 appears to have good activity as a monotherapy in several cancer types expressing TROP2, and thus represents a paradigm-change in the ADC technology.

Fig.2 Schematic diagram of IMMU-132.

What Can We Do for You?

Creative Biolabs is a global leader in delivering customer-centric solutions in the field of ADCs to global clients. We provide various ADC Toxins, ADC Linkers, and Linker-payload Complexes to our clients, and customized combination and synthesis are also available according to the specific demands. Besides, our world-class facilities, backed by a highly experienced team, offer integrated services from ADC Antibody Screening, Antibody Design and Conjugation to ADC in vivo Analysis, ADC in vitro Analysis and ADC Manufacturing. With short lead times to access our services and a customer-centric culture, we strive to offer tailored solutions for every ADC program. If you are looking for ADC development services targeting TROP2, please contact us for more information and a price quote.

Reference

1. Pavšič, M.; et al. The cytosolic tail of the tumor marker protein TROP2-a structural switch triggered by phosphorylation. Scientific reports. 2015, 5: 10324.

For Research Use Only. NOT FOR CLINICAL USE.