ADC Development Services Targeting DLL3

The cell surface Notch ligand delta-like 3 (DLL3) has been identified as a novel putative therapeutic target in high-grade neuroendocrine carcinomas including small cell lung cancer (SCLC),and ongoing studies of anti-DLL3 antibody-drug conjugate (ADC) provide us with a better understanding of the potential of this novel target and ADC therapy, which may offer patients more effective treatment options for SCLC. Creative Biolabs has established diverse technology platforms for ADC design and development. We offer a variety of off-the-shelf Anti-DLL3 ADC Products and customized products to serve your course of ADC development and evaluation.

Introduction of DLL3

DLL3 is a novel target identified in tumor-initiating cells and expressed in more than 80% of patients with SCLC. DLL3 has been implicated in the regulation of cell-fate decisions during development and might function as an oncogenic driver in high-grade neuroendocrine tumors. The DLL3 is the only member of the Notch receptor ligand family that inhibits the Notch receptor pathway. Furthermore, the expression of DLL3 is closely related to neuroendocrine differentiation, and the expression of the transcription factor achaete-scute homolog 1 (ASCL1), which is an important oncogenic driver for SCLC. In preclinical models, DLL3 expression promotes SCLC migration and invasion. Thus, DLL3 protein has emerged as very promising drug target.

The human Notch repertoire. Fig.1 The human Notch repertoire. (Mašek, 2017)

Anti-DLL3 ADC in SCLC

Currently, several DLL3-specific therapies have been developed for the treatment of SCLC, such as the ADC, the bispecific T cell engager immuno-oncology therapy, and the chimeric antigen receptor T cell therapy. As shown in Fig.2, Rovalpituzumab tesirine is a DLL3-targeted ADC that consists of a humanized DLL3-specific IgG1 monoclonal antibody (mAb), a pyrrolobenzodiazepine (PBD) dimer toxin, and a protease-cleavable linker that covalently links the antibody to the toxin. Internalization of the ADC to lysosomes leads to the cleavage of the linker, release of the toxin, and apoptosis. Besides, phase 1 study suggests that rovalpituzumab tesirine is a promising therapy agent for DLL3-positive SCLC.

Structure of Rovalpituzumab tesirine. Fig.2 Structure of Rovalpituzumab tesirine. (Owen, 2019)

What Can We Do for You?

Creative Biolabs has extensive experience in offering perfect customized services for ADC development. We have successfully performed numerous customized ADC preparation projects during the past decade. We possesses unique ADC Antibody Screening platform to screen “internalizing” antibodies which is of highly importance in ADC development. Antibody could be used in the original form or further decorated for ADC conjugation by our Antibody Design and Conjugation platform. At Creative Biolabs, PBD and various Payloads are all available for you, and customized linker-payload complexes could also be obtained by our DrugLnk™ Custom Synthesis services. In addition, Creative Biolabs also supplies further ADC in vivo Analysis and ADC in vitro Analysis for clients all over the world. With enriched experience and advanced technology platforms, Creative Biolabs is committed to providing our clients top-quality services for every component of an ADC. If you need a custom ADC development service or related products, we are more than happy to share our design and experience with you. Please don’t hesitate to contact us for information.

References

  1. Mašek, J.; Andersson, E. R. The developmental biology of genetic Notch disorders. Development. 2017, 144(10): 1743-1763.
  2. Owen, D. H.; et al. DLL3: an emerging target in small cell lung cancer. Journal of hematology & oncology. 2019, 12(1): 61.

For Research Use Only. NOT FOR CLINICAL USE.


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