DLL3 Recombinant Monoclonal Antibody
Description
Definition and Development
DLL3 recombinant monoclonal antibodies are engineered immunoglobulins produced via recombinant DNA technology. They bind specifically to DLL3, a transmembrane protein in the Notch signaling pathway that is highly expressed in SCLC (>80% of cases) but minimally in normal tissues . Key development steps include:
-
Immunogen Selection: Human DLL3 recombinant protein or transfected cell lines .
-
Cloning: Variable regions from immunized animals (e.g., rabbits, alpacas) are cloned into expression vectors .
-
Production: Host cells (e.g., HEK-293T) are transfected for antibody expression, followed by Protein A/G purification .
Mechanism of Action
These antibodies exhibit diverse mechanisms tailored to therapeutic goals:
Key Findings:
-
Bispecific formats induce tumor lysis at sub-picomolar concentrations .
-
ADCs like FZ-AD005 show bystander killing and efficacy in low DLL3-expressing tumors .
-
Trispecific antibodies increase intratumoral T-cell infiltration by 300% compared to bispecifics .
Preclinical Data
Diagnostic Uses
-
Flow Cytometry: Detects DLL3 expression in HEK-293T cells with 1:10,000 dilution .
-
Immunohistochemistry (IHC): Validated in multi-tissue microarrays (TMAs) .
-
Western Blot: Identifies DLL3 at 55–80 kDa in transfected lysates .
Therapeutic Targets
Comparative Analysis of Key Antibodies
Future Directions
-
Combination Therapies: PD-1 inhibitors enhance bispecific antibody efficacy (ORR increase from 23% to 51%) .
-
Biomarker Development: DLL3 expression thresholds (≥50% by IHC) for patient stratification .
-
Next-Gen Formats: Trispecific antibodies with CD137 costimulation to overcome immunosuppressive microenvironments .
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
The DLL3 recombinant monoclonal antibody is meticulously developed through a multi-step process to ensure exceptional quality and specificity. The process begins with the isolation of B cells from the spleen of an immunized animal. These B cells are then exposed to the recombinant human DLL3 protein as an immunogen, stimulating the production of antibodies. The RNA extracted from these B cells is then converted into cDNA through reverse transcription. The DLL3 antibody genes are then amplified using specific primers designed for the antibody constant regions and inserted into an expression vector. This vector is subsequently transfected into host cells, enabling the production of the DLL3 recombinant monoclonal antibody. Following a period of cell culture, the antibody is harvested from the cell culture supernatant and purified using affinity chromatography. This purification process yields a highly purified form suitable for various applications. The antibody's specificity and functionality in detecting human DLL3 protein are rigorously validated through characterization assays, including ELISA and FC analysis.
Target Background
- Research indicates that DLL3 is expressed in tumor specimens from a majority of patients with small cell lung cancer. PMID: 29290251
- Studies have shown that DLL3 expression is silenced in hepatocellular carcinoma (HCC) cells through DNA methylation and is more susceptible to histone acetylation than histone methylation (H3K9me2 or H3K27me3). PMID: 29512761
- Findings suggest that epidermal growth factor-like domain multiple 7 protein participates in the regulation of growth hormone-secreting pituitary adenoma proliferation and invasion through the Notch2/DLL3 signaling pathway. These findings raise the possibility that epidermal growth factor-like domain multiple 7 protein could serve as a valuable biomarker for assessing the invasion and prognosis of growth hormone-secreting pituitary adenomas. PMID: 28705113
- Dll3 was rarely detected in para-carcinoma tissues but was positive in 82.1% of non-small cell cancer tissues. PMID: 28007595
- Both global haplotype and individual haplotype analyses revealed that the haplotypes of SNP1/SNP2/SNP3/SNP4/SNP5 did not correlate with the disease (P >0.05). These findings suggest that genetic variants of the DLL3 gene are not associated with CS in the Chinese Han population. PMID: 27472720
- DLL3 was silenced by methylation in human hepatocellular carcinoma, and it negatively regulates the growth of human hepatocellular carcinoma cells. PMID: 23337976
- Evidence suggests that the three human DLL3 mutations associated with spondylocostal dysplasia are functionally equivalent to the Dll3(neo) null allele in mice. PMID: 11923214
- Mutations in DLL3 cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis. PMID: 12746394
- No novel or previously described mutations were found in a specific cohort, indicating that DLL3 mutations may not be a major cause of congenital scoliosis. PMID: 15717203
- The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity. PMID: 18676613
