The recombinant human DLL3 protein is an active protein produced in mammalian cells. Its production involves the expression of a plasmid containing the target gene that codes for the 429-492aa of the human DLL3. The target gene is fused with a C-terminal 10xHis-tag gene. The purity of the resulting recombinant DLL3 protein is greater than 95% as determined by SDS-PAGE. The biological activity of this DLL3 protein is validated through ELISA, in which it binds to the DLL3 recombinant antibody (CSB-RA882142MA2HU), with the EC50 of 3.990-4.723 ng/mL.
DLL3 is an inhibitory ligand of the Notch receptor pathway [1][2]. It is predominantly localized in the Golgi apparatus and can activate the Notch signaling in trans [3]. Instead, DLL3 can inhibit Notch receptor activation in cis [2].
DLL3 is expressed during brain development where it regulates somitogenesis [2]. In normal tissues, DLL3 has minimal to no surface expression but is abnormally expressed on the surface in 85-94% of small cell lung cancer (SCLC) cases, making it a potential tumor-selective target for SCLC treatment [4]. DLL3 is also expressed in other types of cancer, such as neuroendocrine prostate cancer and Merkel cell carcinoma [1][2]. In these cancers, DLL3 expression is associated with tumor growth and progression.
The regulation of DLL3 expression is complex and involves various signaling pathways. For example, the transcription factor ASCL1 regulates the expression of DLL3 and other Notch signaling proteins in neuroendocrine tumors [2]. Additionally, DLL3 expression can be modulated by the Notch signaling pathway, as DLL3 is a downstream target of Notch activation [5].
References:
[1] H. Xie, F. Kaye, K. Isse, Y. Sun, J. Ramoth, D. French, et al. Delta-like protein 3 expression and targeting in merkel cell carcinoma, The Oncologist, vol. 25, no. 9, p. 810-817, 2020. https://doi.org/10.1634/theoncologist.2019-0877
[2] L. Puca, K. Gavyert, V. Sailer, V. Conteduca, É. Dardenne, M. Sigouros, et al. Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer, Science Translational Medicine, vol. 11, no. 484, 2019. https://doi.org/10.1126/scitranslmed.aav0891
[3] L. Saunders, A. Bankovich, W. Anderson, M. Aujay, S. Bheddah, K. Black, et al. A dll3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo, Science Translational Medicine, vol. 7, no. 302, 2015. https://doi.org/10.1126/scitranslmed.aac9459
[4] X. Nie. Delta‐like ligand 3: a promising target against small cell lung cancer, Aging Medicine, vol. 7, no. 3, p. 283-286, 2024. https://doi.org/10.1002/agm2.12311
[5] D. Jia, J. Underwood, Q. Xu, & Q. Xie. Notch2/notch3/dll3/maml1/adam17 signaling network is associated with ovarian cancer, Oncology Letters, 2019. https://doi.org/10.3892/ol.2019.10170
