Anti-FAP Antibody Development

Creative Biolabs provides customized antibody preparation services against fibroblast activation protein (FAP) by our advanced technology platform to help your projects. Our professional scientists have extensive experience in antibody production, and bio-conjugation and are committed to providing high-quality services to promote the monoclonal antibody (mAb) development of innovative cancer treatments.

Fibroblast Activation Protein

A key characteristic of carcinoma-associated fibroblasts (CAFs) is the expression of fibroblast activation protein (FAP) α. FAP is a type II transmembrane protein which has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. FAP expression is difficult to detect in non-diseased adult organs but is greatly upregulated in sites of tissue remodeling, which include liver fibrosis, lung fibrosis, atherosclerosis, arthritis, tumors, and embryonic tissues. Due to its restricted expression pattern and dual enzymatic activities, FAP is emerging as a unique therapeutic target. FAP plays a role in matrix digestion and invasion through its gelatinase activity. Inhibiting the expression and/or activity of FAP in CAFs attenuated tumor growth, decreased angiogenesis, improved intratumoral drug delivery and/or restored anti-tumor immune responses. The identification of FAP as a target selectively expressed on fibroblasts within the tumor stroma or on CAFs led to intensive efforts to exploit this novel cellular target for clinical benefit.

Fig.1 FAP domain structure.

Antibody Therapy against FAP

FAP-based CAF-targeting therapeutic approaches using their neutralizing antibodies, inhibitors, prodrugs and DNA vaccine showed attenuation in tumor growth via improving tumoral immune response in different experimental mouse tumor models. To extend the FAP expression-based CAF targeting approach sufficiently to allow a preclinical study, an anti-FAP mAb was covalently linked with DM1, a tubulin-binding maytansinoid with antimitotic activity, known as FAP5-DM1. FAP5-DM1 shows an impressive level of therapeutic benefit, with rapid onset of action, complete responses, and long-lasting suppression of tumor growth.

Fig.2 Structural representation of FAP5-DM1. (Ostermann, 2008)

FAP is a post-prolyl protease with distinct substrate requirements, and its expression is restricted to the surface of reactive fibroblasts localized to the tumor microenvironment in normal, healthy adults. At present, these two characteristics make FAP uniquely suited for therapeutic strategies aimed at targeting CAFs. The surge in both pharmaceutical and academic efforts to develop FAP as a therapeutic target offers a promising outlook for negating that statement in the not-so-distant future.

Creative Biolabs has gained significant knowledge in mAbs preparation. We are more than happy to share our experience and help our customers with this important antibody generation step. Please feel free to contact us for more information about anti-FAP antibody development services and a detailed quote.

Reference

1. Ostermann, E; et al. Effective immunoconjugate therapy in cancer models targeting a serine protease of tumor fibroblasts. Clinical cancer research. 2008, 14(14), 4584-4592.

For Research Use Only. NOT FOR CLINICAL USE.