>Newly Launched FLAG Claudin Family Proteins Facilitate Innovative Drug Development
ACROBiosystems has successfully launched its Claudin family proteins, including Claudin 18.2, Claudin 18.1, Claudin 6, and Claudin 9. Generally, these full-length multi-pass transmembrane target antigens are difficult to prepare while maintaining their native conformation. However, using its Full-Length Active Gallery (FLAG) technology, ACROBiosystems’ has developed a series of multi-pass transmembrane protein development platforms including virus-like particles (VLP), detergent micelles and Nanodiscs. This allows us to offer full-length Claudin family proteins with high bioactivity and batch-to-batch consistency that has been verified through ELISA, SPR, BLI, FACS, and other methods, to support innovative drug research and development.
The Claudin protein family is a critical component of tight junctions (TJs). These TJs exist in the junctional complex of epithelial and endothelial cells, which plays a crucial role in cell polarity, adhesion, and permeability. Tissue structure integrity, transmembrane movement, and signal transduction inside and outside of cells are regulated by TJs. When the integrity of TJs is compromised, increased bypass permeability occurs which can directly lead to the perfusion and extravasation of cancer cells through the endothelial barrier.
Structure of TJs
Recent studies have shown that abnormal expression of Claudin family proteins, as a key component of TJs, is closely related to the occurrence, development, and prognosis of tumors, thus making them ideal therapeutic targets.
Structure of Claudin
For example, Claudin 18.2 is a therapeutic target for solid tumors such as gastric cancer and pancreatic cancer due to its high specificity and stable expression. Currently, the development of drugs targeting Claudin 18.2 cover various forms such as monoclonal antibody drugs, bispecific antibodies, ADCs, and CAR-T cell therapy.
Similarly, Claudin 6 is always highly expressed in tumor tissues in liver cancer, ovarian cancer, endometrial cancer, and esophageal cancer but not in surrounding normal tissues. This makes it another significant target for tumor therapy. Finally, Claudin 9 is another potential target that is abundantly expressed in the anterior pituitary gland. The overexpression of Claudin 9 is closely related to the invasion of pituitary oncocytoma, occurrence and progression of gastric cancer, cervical cancer, and lung cancer metastasis, and can serve as a diagnostic and prognostic marker for these cancers as well as an immunotherapy.
Although many Claudin family proteins are potential therapeutic targets, it is extremely difficult to obtain biologically active soluble antigens due to their structural complexities such as multiple hydrophobic transmembrane regions. This seriously hinders the development of drugs and therapies targeting Claudin proteins. Like other multi-pass transmembrane proteins, the expression level of recombinant four-pass Claudin proteins is much lower than other soluble proteins due to cell membrane surface area and potential cytotoxicity of overexpressed membrane proteins.
ACROBiosystems has made a concerted effort to design and optimize the expression interval, expression system, and culture conditions, and using our proprietary FLAG technology, can now provide sufficient quantity of Claudin 18.2, Claudin 18.1, Claudin 6, and Claudin 9 for immunization and drug development. Our Claudin family stabilized structures and high activity to facilitate innovative drug and therapy development as well as mechanism studies.
1. Du H, Yang X, Fan J, et al. Claudin 6: Therapeutic prospects for tumors, and mechanisms of expression and regulation[J]. Molecular Medicine Reports, 2021, 24(3): 1-9.
2. Sharma, R.K., Chheda, Z.S., Das Purkayastha, B.P. et al. A spontaneous metastasis model reveals the significance of Claudin 9 overexpression in lung cancer metastasis. Clin Exp Metastasis 33, 263–275 (2016). https://doi.org/10.1007/s10585-015-9776-4
3. Higashi, A.Y., Higashi, T., Furuse, K. et al. Claudin 9 constitute tight junctions of follicular-stellate cells in the anterior pituitary gland. Sci Rep 11, 21642 (2021). https://doi.org/10.1038/s41598-021-01004-z
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