ADC Development Services Targeting MUC16

Antibody-drug conjugates (ADCs) represent a type of novel targeted immunotherapy that utilizes potent cytotoxic drugs linked to antibodies through chemical linkers. This approach can significantly improve the efficacy of drug by specifically delivery the payload to cancer cells while reducing side effects to healthy cells.

Creative Biolabs has constructed mature ADC technology platforms and innovative conjugation methods to produce stable ADC candidates that present high anti-tumor efficacy. At present, we offer a full range of ADCs development services targeting the MUC16 antigen.

Introduction of MUC16

MUC16, also known as CA125, is a type I transmembrane mucin encoded by the MUC16 gene. It belongs to the mucin family, and is a large glycoprotein containing 22,152 amino acids. MUC16 consists of an O-glycosylated N-terminal domain, a tandem repeat domain, a transmembrane domain and a cytoplasmic tail. The O-glycosylated protein functions in producing a protective mucous barrier to protect epithelial cells from pathogens. It is also considered as a biomarker for different cancers diagnosis and treatment with high expression levels in cancer cells. MUC16 as a clinical target has been widely investigated in three distinct clinical scenarios, including as a screening test for the early diagnosis of ovarian cancer (OC), to distinguish the diseases progress from benign to malignant in patients with pelvic masses, and to monitor response to therapy in women with OC.

Fig.1 Model for MUC16-induced NK cell inhibition. (Felder, 2014)

Anti-MUC16 ADC in OC andPancreatic Cancers

OC and pancreatic cancer (PC) are the seventh and eighth most common cancer causing death in the world, respectively. MUC16 is highly expressed in human epithelial OCs and PCs, but it is not found in normal cells. Moreover, MUC16 has been found to inhibit NK cell-mediated antitumor cytotoxic responses via improving the binding of tumor cells to mesothelial cells in the peritoneal cavity. Therefore, MUC16 is a useful target in targeted immunotherapy such as the ADCs.

Sofituzumab vedotin (also known as RG7458 or DMUC5754A) is an ADC consisting of a humanized IgG1 anti-MUC16 monoclonal antibody conjugated to the potent anti-mitotic agent, monomethyl auristatin E (MMAE) via a protease-labile linker. Preclinical trial results showed that sofituzumab vedotin can specifically bind to the MUC16 extracellular domain and present potent antitumor activity in MUC16-positive OC and PC mouse xenograft models. Besides, the ADC has a favorable safety profile to normal cells. Based on positive pre-clinical data, sofituzumab vedotin has been investigated in clinical phase I trial in patients with platinum-resistant OC or unresectable PC.

Fig.2 Structure of sofituzumab vedotin.

Our Comprehensive ADCs Development Services

Targeted delivery of potent drug into cancer cells to improve the outcome is considered as a promising strategy. ADCs represent the promising class of anticancer therapeutic agents, being one of the fastest growing fields in cancer therapy. Creative Biolabs is a leader in the field of antibody and antibody related drug discovery and development for many years. We have developed first-class conjugation technology platform to perform the effective antibody-drug conjugation. Our ADCs construction services include ADC Antibody Screening, DrugLnk™ Custom Synthesis, Antibody Design and Conjugation, ADC in vitro Analysis and ADC in vivo Analysis. If you are interested in our services, please contact us to get an ADC development service quote now.

Reference

1. Felder, M.; et al. MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress. Molecular cancer. 2014, 13(1): 129.

For Research Use Only. NOT FOR CLINICAL USE.