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Key Steps in Antibody Discovery for ADC
The key to ADC antibody discovery is selecting a highly specific, high-affinity antibody
that efficiently internalizes to deliver a cytotoxic payload, while being stable and suitable for chemical conjugation.
Target Antigen Selection & Validation
Identifying a surface antigen that is highly and homogeneously expressed on cancer cells but has minimal expression on healthy tissues. This is crucial for maximizing efficacy and minimizing off-target toxicity.
Screening for High Binding Affinity & Specificity
Selecting antibodies that bind tightly and specifically to the target antigen. High affinity enhances the potency of the ADC at the tumor site.
Assessing Rapid and Efficient Internalization
This is a critical step for ADCs. The antibody must be quickly internalized by the cancer cell upon binding to its target. This is measured using specialized cellular assays to ensure the cytotoxic payload can be delivered inside the cell.
Evaluation of Intracellular Trafficking
Confirming that once internalized, the antibody-antigen complex is trafficked to the lysosome. This is essential for the cleavage of most linker chemistries and the subsequent release of the active payload.
Analysis of Conjugation Suitability & Developability
Assessing the antibody's stability, solubility, and ensuring it has appropriate amino acid residues (e.g., cysteines, lysines) for stable and consistent conjugation of the linker-payload, leading to a homogenous product.
What Our Antibody Discovery Service Offers
Antibody Screening for ADC Development
High-throughput screening to identify optimal antibodies with high specificity, affinity, and internalization efficiency.
- Diverse antibody libraries: Phage display, hybridoma, single B-cell, and synthetic libraries.
- Focus on ADC-specific properties: Target binding affinity, efficient internalization into target cells, and compatibility with linker-payload conjugation.
Antibody Engineering & Optimization
- Humanization & Affinity Maturation: Improves antibody efficacy and reduces immunogenicity.
- Fc Engineering: Modifies Fc regions to enhance ADCC, CDC, or serum half-life as needed.
- Conjugation Site-Specific Engineering: Ensures stable and homogeneous drug-antibody linkage (e.g., cysteine or site-specific conjugation).
Featured Tumor Protein Discovery Services
Drawing upon years of experience and insights from the latest tumor treatment research trends, Creative Biolabs has launched specialized antibody discovery services for oncology, designed to accelerate the development of more effective tumor therapies and better serve our clients.
Tumor Surface Protein Specific Antibody Discovery
Targeting surface proteins to ensure direct delivery of cytotoxic agents to cancer cells while minimizing systemic toxicity.
Tumor Microenvironment Antigen Specific Antibody Discovery
Developing antibodies against unique antigens within the TME to overcome drug resistance and enhance therapeutic efficacy.
Key Antibody Discovery Platforms at Creative Biolabs
Phage Display Platform
Our Phage Display Platform is a powerful and versatile tool for antibody discovery and engineering. It enables the rapid screening of large libraries of antibody fragments (such as scFv and Fab), allowing for efficient identification of high-affinity binders against a wide range of targets.
Antibody Humanization Technology
Our technology is designed to reduce immunogenicity while preserving the binding affinity of non-human antibodies. We precisely graft the CDRs of murine antibodies onto human frameworks using advanced computational modeling.
Internalizing Antibody Screening Platform
Using high-throughput screening assays, including flow cytometry and fluorescence microscopy, we rigorously evaluate internalization efficiency, ensuring the selection of antibodies with optimal intracellular delivery properties.
Antibody Discovery Service Workflow
Target Identification and Validation
- Bioinformatics & Target Prioritization: Leverage in silico tools to analyze target expression profiles, tumor specificity, and internalization potential.
- Humanized Mouse Models: Utilize target-humanized mouse models for target validation and mechanistic studies.
- Cell Panel Screening: Establish target-expressing cell lines to evaluate antigen accessibility and internalization kinetics.
High-Throughput Antibody Discovery
- Diversified Antibody Libraries: Access fully human antibody libraries or immunize transgenic platforms.
- Single-Cell Screening: Implement microfluidic platforms to screen >500,000 cells/day for antigen binding and internalization.
- Functional Prioritization: Use pH-sensitive probes to simultaneously assess antigen binding and internalization efficiency during primary screening.
Antibody Characterization and Optimization
- Affinity Maturation: Employ yeast/mammalian display to fine-tune binding characteristics.
- Epitope Binning: Map epitopes to identify non-competing clones suitable for bispecific ADCs.
- Developability Assessment: Evaluate stability (DSC), aggregation propensity (DLS), and polyspecificity (SPR) to eliminate problematic candidates.
Internalization and Payload Compatibility Testing
- Quantitative Internalization Assays: Implement high-content imaging or flow cytometry with pH-sensitive dyes to rank antibodies by internalization rate.
- Early-Stage Tox Screening: Use immune-humanized models to assess on-target/off-tumor effects.
- Payload-Linker Compatibility: Test unconjugated antibodies with various linker-payload chemistries using surrogate assays.
ADC Assembly and Preclinical Evaluation
- Modular Conjugation Services: Offer rapid DAR2-8 ADC preparation with various linker-payloads.
- In Vivo Efficacy Models: Utilize CDX/PDX models in target-humanized mice for pharmacodynamic evaluation.
- Toxicity Profiling: Conduct non-GLP studies in relevant species with payload-focused toxicology endpoints.
Report Delivery and Data Management
- Standardized Reporting: Provide milestone reports with raw/processed data and comparative benchmarking against reference ADCs.
- Interactive Data Platforms: Deliver web-based dashboards for real-time tracking of antibody screening and characterization data.
- Post-Delivery Support: Offer expert consultations, tech transfer packages for scale-up, and long-term data archiving.
Why Choose Creative Biolabs?
Creative Biolabs’ services are designed to accelerate the development of high-potency, clinically viable ADCs with optimized efficacy and safety.
- Extensive experience in oncology and ADC development.
- Flexible platforms for both fully human and engineered antibodies.
- Integrated services from antibody discovery to preclinical ADC evaluation.
Advanced Antibody Solutions Trusted by Leading Researchers
What Our Customers Say About Us
Unlock Comprehensive Insights with Our ADC Case Studies
ADC Clinical Trial Review
This document introduced a list of FDA-approved ADCs and provided a thorough analysis of international ADC clinical trials as well as our outlook on trends in the next ADC advancements.
The following list includes the major topics of this brochure:
- Overview of the FDA-approved ADCs
- Overview of ADCs in Clinical Trials
- Selected Targets for ADCs in Clinical Trials
- Indications
- Status of ADCs Clinical Trials
- Companies and Institutions
- Summary and Outlooks
Anti-HER2 ADC Preparation & Potency Evaluation
HER2 is a crucial target in cancer therapy, and developing effective HER2-ADCs holds great promise for treating HER2-positive cancers. This case study delve into key aspects such as optimized strategies for HER2 antibody selection, linker-payload conjugation techniques, in vitro and in vivo potency assessment data, and solutions to challenges encountered during development.
The following list includes the main content:
- Introduction
- Materials and Methods
- Results
Custom Synthesis of ADC Linker-payload SET
At Creative Biolabs, many unique compounds have been designed to fulfill clients' special requirements, ranging from traditional payload-linkers containing auristatin or maytansinoid derivatives to more novel warheads such as topoisomerase inhibitors. Presented here is a case study for the synthesis of two customized payload-linker complexes via the "DrugLnk" organic synthesis services.
The following list includes the main content:
- Introduction
- SN38: a novel payload for ADC development
- Case 1: Mc-vc-PAB-SN38
- Case 2: CL2A-SN38
- Conclusions
Antibody Internalization Assay
Creative Biolabs has adopted and perfected several techniques to study antibody and ADC internalization. These case studies are presented in three parts: the chemical structure of ADCs, the measuring method, and the findings. With the success of these case studies, various approaches have been proven helpful in detecting internalization efficiency and are elucidated in this brochure.
Three case studies are listed as follows:
- Case 1: Internalization and intracellular trafficking of anti-HER2 mAb-vc-Toxin (NGL-Z1 ADC)
- Case 2: Cellular internalized and lysosome trafficking of anti-HER2 mAb and anti-HER2 mAb-vc-MMAE
- Case 3: Internalization kinetics and intracellular trafficking of anti-Trop mAb-vc-auristatin analogue
FAQs About Our Antibody Discovery Services
Q: What types of antibodies can Creative Biolabs discover for ADC development?
A: We can discover a wide range of antibody formats, including monoclonal antibodies (mAbs), single-domain antibodies (sdAbs), and bispecific antibodies, all optimized for ADC conjugation and function.
Q: How long does the antibody discovery process typically take?
A: The timeline varies depending on the complexity of the target and the specific service package, but our streamlined workflows are designed for rapid turnaround, often significantly reducing industry standard timelines.
Q: Can you help with target selection for ADC development?
A: While our primary focus is antibody discovery, our scientific team can provide consultation and insights into potential ADC targets based on their biological relevance and expression profiles.
Q: What quality control measures are in place for the antibodies you discover?
A: We implement rigorous quality control at every stage, including comprehensive binding assays, functional validation, purity assessment, and stability testing, to ensure the delivery of high-quality, reliable antibodies.
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