Anti-Collagen IV Antibody Development

As a well-recognized leader with over a decade of experience in monoclonal antibodies (mAbs) preparation, Creative Biolabs is dedicated to the development of new therapeutic agents. Collagen IV is the most abundant constituent of basement membranes (BMs), accounting for up to 50% of the structural elements and forms a polygonal network. Collagen IV networks endow BMs with a tensile strength sufficient to protect tissues from mechanical stress and to determine their architecture. Through in-depth study of collagen IV, Creative Biolabs now offers our honor clients customized anti-collagen IV antibody development services.

Collagen IV

Pancreatic cancer is a disease with extremely poor prognosis. The five-year survival rate has only improved marginally over the past decades and remains at less than 5%. Cancer cells actively participate in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Collagen IV is highly expressed by pancreatic cancer cells both in vivo and in vitro. It can be made from six different α-chains, α1(IV) to α6(IV), which appear in different combinations to form triple helical molecules called protomers that further organize into a sheet-like structure in the BM. However, the α5(IV) and α6(IV) chains are lost from the BM in the pancreatic duct in cancer, and high levels of α1(IV) and α2(IV) chains are expressed in the tumor stroma. Collagen IV not only provides a scaffold for assembly and mechanical stability, but also important in cell adhesion, migration, survival, proliferation, and differentiation. The integrin signaling pathway activated in a tumor environment with collagen deposition is responsible for low cell elasticity and high metastatic ability.

Fig.1 Structure of human collagen IV. (Ortega, 2002)

Antibody Development

Collagen IV has been proposed as a promising antibody-drug conjugate (ADC) target. For instance, a therapeutic approach was developed by using ADC targeting tumor stromal collagen IV. This ADC was composed of SN-38 conjugated to an anti-collagen IV mAb via a pegylated linker bearing an acidic-sensitive ester bond. A successful highly localized concentration in the tumor was achieved, with the ADC selectively extravasated from leaky tumor vessels and bound to the stroma to create a scaffold. From this, SN-38 underwent sustained release, followed by diffusion throughout the tumor tissues, leading to damage to both tumor cells and vessels.

Fig.2 Formula of non-internalizing mAb-camptothecin conjugate targeting the collagen IV of the stromal barrier. (Joubert, 2017)

Creative Biolabs has gained significant knowledge in antibody preparation. We are glad to share our experience and help our customers with antibody development for collagen IV antigen. Please feel free to contact us for more information and a detailed quote.

References

1. Ortega, N.; Werb, Z. New functional roles for non-collagenous domains of basement membrane collagens. Journal of cell science. 2002, 115(22), 4201-4214.
2. Joubert, N.; et al. Towards antibody-drug conjugates and prodrug strategies with extracellular stimuli-responsive drug delivery in the tumor microenvironment for cancer therapy. European Journal of Medicinal Chemistry. 2017, 142.

For Research Use Only. NOT FOR CLINICAL USE.