Antibody drug conjugates (ADCs) are a uniquely targeted cancer therapy that combines the direct tumor targeting capability of monoclonal antibodies together with the potency of cytotoxic drugs. Alfa Cytology offers cutting-edge services in the development of ADCs for pancreatic cancer, with a focus on providing innovative preclinical research solutions.
Advantages of Antibody Drug Conjugates (ADCs)
ADC selectively binds to cancer cell antigens, chemically linking the antibody to the cytotoxic drug through a stable junction that combines the specificity of a monoclonal antibody with the potent cell-killing ability of a cytotoxic drug, which enables tumor-specific delivery of potent cytotoxicity, while decreasing the extra-tumor toxicity associated with traditional cytotoxic chemotherapy, thereby increasing the therapeutic window.
Fig. 1 Structure of ADCs and specific components of ADCs in development for targeting pancreatic cancer. (Wittwer, N.L, et al, 2023)
Components of Antibody Drug Conjugate (ADC)
Each component of the ADC can be customized to meet a range of pharmacological and clinical requirements. An ADC consists of three distinct parts:
- A tumor-targeting monoclonal antibody (mAb) that specifically binds to a tumor-associated antigen
- A highly potent cytotoxic drug (known as a payload)
- A chemical linker
Key ADC Candidates in Development for Pancreatic Cancer
| Antibody Drug Conjugate | Cytotoxic Drug | Target | Phase |
|---|---|---|---|
| Trastuzumab Deruxtecan | Deruxtecan (a topoisomerase I inhibitor) | HER2 (Human Epidermal Growth Factor Receptor 2) | Phase III |
| Mirvetuximab Soravtansine | DM4 (a maytansinoid) | FRα (Folate Receptor Alpha) | Phase II |
| Enfortumab Vedotin | MMAE (Monomethyl Auristatin E) | Nectin-4 | Phase III |
| AZD-9150 | Monomethyl Auristatin E (MMAE) | CD-70 (Cluster of Differentiation 70) | Phase II |
| XmAb®20717 | PBD (Pyrrolobenzodiazepine) dimer | B7-H3 | Phase I |
| Depatuxizumab Mafodotin | MMAF (Monomethyl Auristatin F) | EGFR (Epidermal Growth Factor Receptor) | Phase I |
| Enapotamab Vedotin | MMAE (Monomethyl Auristatin E) | AXL receptor tyrosine kinase | Phase I |
| DMUC5754A | MMAE (Monomethyl Auristatin E) | MUC16 (Mucin 16) | Phase I |
Our Services
By leveraging extensive expertise in basic pancreatic cancer research, Alfa Cytology ensures the highest quality and efficiency in ADC development, facilitating the advancement of promising therapeutic candidates from early-stage research to preclinical validation.
Target Antigen of ADC Development
Our ADC development service targets several key antigens associated with pancreatic cancer. These targets are chosen based on their high expression in tumor tissues and low expression in normal tissues, ensuring specificity and minimizing off-target effects. Key targets include:
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Antibody Drug Conjugate (ADC) Types We Offer
Monoclonal ADC
Utilize highly specific monoclonal antibodies for precise targeting of PC antigens.
Features: High specificity and minimal off-target effects, enhanced targeting accuracy and reduced systemic toxicity.
Bispecific ADC (BsADCs)
Employ bispecific antibodies that target two different antigens on pancreatic cancer cells.
Features: Dual targeting capability, improved tumor specificity and reduced likelihood of resistance.
Single-domain ADC
Involve single-domain antibodies (VHHs) for targeting pancreatic cancer antigens.
Features: Small size, deep tissue penetration, better tumor penetration and faster clearance from non-target tissues.
Antibody Fragment-drug Conjugates (FDCs)
Conjugate cytotoxic drugs to antibody fragments, such as Fab or scFv, for PC therapy.
Features: Smaller molecule size, better tumor penetration, improved pharmacokinetics and reduced immunogenicity.
Workflow of Antibody Drug Conjugate (ADC) Development
Our development process for ADCs follows a meticulous and systematic approach to ensure the highest standards of efficacy and safety. The process includes the following steps:
Target Identification
Comprehensive analysis to identify and validate appropriate targets specific to pancreatic cancer cells.
Antibody Generation
Development and selection of high-affinity antibodies against the identified targets.
Conjugation Chemistry
Optimization of linker and drug conjugation methods to ensure stable and effective ADCs.
In vitro Testing
Extensive in vitro assays to evaluate the binding specificity, cytotoxicity, and mechanism of action of the ADCs.
In vivo Testing
Preclinical animal studies to assess the efficacy, pharmacokinetics, and safety profile of the ADCs.
Antibody-drug conjugates represent a revolutionary advancement in targeted cancer therapy, combining the specificity of antibodies with the potent cytotoxic effects of chemotherapy agents. Alfa Cytology's ADC development services for pancreatic cancer provide comprehensive support from initial target identification to preclinical validation, ensuring the highest quality and efficiency in developing promising therapeutic candidates. For more information or to discuss specific project needs, please contact us.
Reference
- Wittwer, N.L., et al. Antibody drug conjugates: hitting the mark in pancreatic cancer? J Exp Clin Cancer Res. 2023, 42: 280.
