Anti-Laminin α5 Chain Antibody Development

As a well-recognized leader with over a decade of experience in antibody preparation, Creative Biolabs and our collaborators have established manufacturing platforms and pipelines fully designated for monoclonal antibodies (mAbs) preparation. We are dedicated to the development of new therapeutic agents and offer our clients with comprehensive high-quality services for antibody preparation against laminin α5 chain.

Laminin

Laminins, a large family of αβγ heterotrimeric proteins mainly found in basement membranes (BMs), are strong promoters of adhesion and migration of multiple cell types, such as tumor and immune cells, via several integrin receptors. Laminins play important roles in tissue morphogenesis and homeostasis by regulating tissue architecture, cell adhesion, migration, and matrix-mediated signaling. Laminin heterotrimers are relatively large proteins with a molecular weight (MW) ranging from 400 to 900 KDa and exist as cross-shaped molecules with two or three short arms and one long arm. To date, five α, three β, and three γ laminin chains assemble into more than 15 laminin isoforms. Among human laminin α (LMα) chains, LMα5 is the largest of all laminin chains with an approximately MW of 350 KDa and the most widely expressed LMα chain in adult life. Besides, α5 is unique in containing functional Arg-Gly-Asp-(RGD) sequence. LMα5 constitutes laminin-511, 512, 513, and is present in epithelial BM (laminin-511) and vascular endothelial BM (laminin-511 and laminin-521). Especially, laminin-511 contributes to tumor dissemination and metastasis in advanced breast carcinomas and other tumor types.

Fig.1 Laminin subunits and examples of three heterotrimers. (Hamill, 2009)

Antibody Strategy

Following their secretion and deposition, laminins interact with several matrix proteins, including entactin, the heparan sulfate proteoglycans perlecan and agrin, the netrins and collagen VII, and this might affect laminin deposition. Laminin α5 in the BM supports strong adhesion of endothelial cells via β1 integrins, ensuring the correct cortical tension and stabilizes VE-cadherin at cell-to-cell junctions, required for a normal shear response (figure 2 shown).

Since many research teams have already developed the different formats of mAbs that specifically bind to LMα5, the chain-specific antibodies should be used in another appropriate way to perform their original functions in tumor treatment. Antibodies can not only disturb the function of the protein itself but also be conjugated with drugs. Antibody-drug conjugates (ADCs) release the cytotoxic payload and initiate tumor cell death. Dying cells subsequently release high concentrations of reducing agents from their intracellular compartments into the surrounding environment, thus triggering the additional release of drug in a self-amplifying fashion. The release of cytotoxic payload in the extracellular environment may facilitate a by-stander effect, as the drug can diffuse and internalize in neighboring cells.

Fig.2 Central role of LMα5 in shear response of resistance arteries. (Di Russo, 2016)

Features

• Cost-effective
• Fast turnaround time and competitive pricing
• Personalized and comprehensive services
• Advanced technologies

Creative Biolabs provides customized antibody development as well as bioconjugation services for LMα5 by our advanced technology platform to help your projects. If you are interested in our services, please feel free to contact us for more details.

References

1. Hamill, K. J.; et al. Laminin deposition in the extracellular matrix: a complex picture emerges. Journal of Cell Science. 2009, 122 (24), 4409-17.
2. Di Russo, J.; et al. Endothelial basement membrane laminin 511 is essential for shear stress response. The EMBO journal. 2016 36 (2), 183-201.

For Research Use Only. NOT FOR CLINICAL USE.