CD46 Specific Neutra™ Antibody Products
Product listCD46 (cluster of differentiation 46, aliases CD46 complement regulatory protein, MCP, MIC10, etc.) is a type one transmembrane protein encoded by the CD46 gene (~43 kb, containing 14 exons) participating in the complement system. CD46 is ubiquitously expressed in almost all types of cells and is initially recognized as a binding protein of C3b and C4b in human peripheral blood cells, serving as a cell surface receptor, taking essential roles in the adaptive and innate immune responses.
Its Gene ID: 4179, UniProtKB ID: P15529, and OMIM ID: 120920.
CD46 Functions and Signaling Pathways
CD46 is widely recognized as an inhibitory receptor that binds to and inactivates C3b and C4b, the two pivotal activation fragments in the alternative pathway (AP), which covalently deposit on host cells of self-tissue. CD46 acts as a cofactor for serine protease factor I (FI)-mediated cleavage of C3b and C4b to prevent their further engagement by the activation pathways, protecting the host cell from damage by complement.
Fig.1 Cofactor activity of CD46 illustrated for the alternative pathway.1, 3
CD46 also plays the role of metabolic driver. It is demonstrated that CD46 drives cell survival and metabolism together with intracellular C3, which is biosynthetically derived or can be loaded from the plasma. Besides, it is reported that STAT3 activates the promoter of CD46, thus increasing IL-6 with the co-stimulation of CD46 with the existence of C3(H2O). The CD46-STAT3-C3 axis conducts regulation on metabolic and regenerative processes and is involved in various tumors.
Fig.2 Intracellular C3 and CD46 drive cell metabolism and survival.2, 3
CD46 also plays a role in the autophagy of human reproduction systems. Moreover, CD46 has been recognized as a receptor for 11 pathogens. It is revealed that its deficiency results in inflammatory disorders, while its overexpression in various cancers and some adenovirus infections contributes to its targeting by oncolytic agents and adenoviral-based therapeutic vectors.
CD46 as a Therapeutic Target
The diversified and essential functions of CD46 make it emerge as an attractive therapeutic target for research and clinical purposes. There are dozens of CD46-targeting therapeutic agents, including antibodies and oncolytic adenoviral- /measles virus-based vectors, being evaluated in research and clinical trials. Besides, over 500 CD46-based gene therapy trials have been conducted, in which human adenoviral vectors are mainly utilized.
CD46-based antibody-drug conjugate (ADC) therapy, applying an antibody to mediate the CD46-targeting specificity, has also attracted much attention these years and several projects are undergoing clinical trials. The effectiveness of CD46-ADC has been demonstrated in multiple myeloma in a mouse model, in which significant inhibition of myeloma cell proliferation is observed. It is also found in a case that a tubulin inhibitor conjugated as the ADC added to a micropinocytosis anti-CD46 antibody exhibits efficacy in metastatic castration-resistant prostate cancer.
Creative Biolabs offers different anti-CD46 antibody products. These antibodies are recombinantly expressed and could be used for various purposes. Customization of CD46-based neutralizing antibodies is also available for you here.
REFERENCES
- Liszewski, M. Kathryn, and John P. Atkinson. "Complement regulator CD46: genetic variants and disease associations." Human genomics 9 (2015): 1-13.
- Elvington, Michelle, M. Kathryn Liszewski, and John P. Atkinson. "CD46 and oncologic interactions: Friendly fire against cancer." Antibodies 9.4 (2020): 59.
- Under open access license CC BY 4.0, without modification.
