Antibody Drug Conjugate Development Services
As a hotspot of anti-cancer drug development, antibody-drug conjugates (ADCs) are usually formed by covalently linking monoclonal antibodies (mAbs) to cytotoxic drugs via chemical linkers, which combine the advantages of high specific targeting ability and potent killing effects. Alfa Cytology provides antibody drug conjugate development services to help customers realize precise and efficient cancer cell elimination.
Introduction to Antibody Drug Conjugate
Chemotherapy based on cytotoxic drugs has been the mainstay of therapy for various cancers for decades. However, most of these chemotherapeutic agents have a low therapeutic index, and severe side effects are usually due to drug exposure to non-specific target tissues.
Fig.1 The structure and characteristics of an ADC drug. (Fu, Z., et al., 2022)
On the other hand, the emergence of mAb has changed the paradigm of cancer therapy by precisely targeting tumor surface antigens. However, therapy with mAb alone is often ineffective compared to chemotherapy.
As a result, a new concept called antibody drug conjugates has emerged to bridge the gap between mAb and cytotoxic drugs to improve the therapeutic window. With expanding targets and indications, ADCs are ushering in a new era of targeted cancer therapy and are expected to replace conventional chemotherapy in the future.
Our Services
Alfa Cytology understands the dynamics and complexities of the current ADC technology landscape and is well-versed in various ADC technologies. We utilize our expertise to identify and map the appropriate design space for the development of your ADCs for cancer therapeutics.
Antibody Development and Screening Services
Tumor-targeting antibodies are important for specific binding between target antigens and ADCs. In addition to high binding affinity to the target antigen, the ideal antibody portion should also promote effective internalization, exhibit low immunogenicity, and maintain a long plasma half-life. Alfa Cytology considers several factors such as affinity, specificity, tumor penetration, and half-life to provide customers with the optimal tumor-targeting antibodies.
Cytotoxic Payload Screening and Optimization Services
Cytotoxic payloads are warheads that exert cytotoxicity after ADC internalization into cancer cells. Payload compounds need to be highly potent, stable under physiological conditions, and have functional groups that can be conjugated to antibodies. We offer several different classes of payloads, including traditional cytotoxic payloads, including potent microtubule protein inhibitors and DNA damaging agents, as well as payloads with novel mechanisms, such as small molecule immunomodulators.
Linker Design and Optimization Services
The linker in the ADC bridges the antibody to the cytotoxic drug. It is one of the key factors associated with ADC stability and payload release profile, which is therefore important for the ultimate therapeutic index of the ADC. We provide design and synthesis services for ADC linkers and linker-drug conjugates. Depending on the drug release mechanism, we design and synthesize different ADC linkers, including cleavable and non-cleavable linkers, self-incinerating tracer-free linkers, and peptide linkers.
Conjugation Approaches Services
In addition to the choice of antibody, linker, and payload, the method by which the small molecule portion, i.e., the junction plus the payload, is conjugated to the antibody is also important for the successful construction of ADCs. Our team provides efficient ADC conjugation services to accelerate the production of ADC constructs with superior properties. Our techniques include, but are not limited to, amine (Lys) conjugation, thiol (Cys) conjugation, site-specific conjugation, enzyme conjugation, sugar conjugation, and click chemistry.
Workflow of Antibody Drug Conjugate Development
01. Target Selection
Selection of cancer-associated antigens suitable as ADC targets.
02. Component Selection
Selection of the antibody, cytotoxin and linker for following ADC synthesis.
03. Synthesis of ADC
Chemical reaction of the selected antibody with the linking drug to form ADC.
04. ADC Characterization
Evaluate ADCs for purity, stability, solubility and dissolution.
05. Preclinical Evaluation
The ADME/PK.antitumor activity, efficacy, and other properties are assessed.
Candidate ADC Drug
Our Advantages
Largest Toolbox
Strong Expertise
One-stop Solution
Short Turnaround
Altering any of the three crucial components can significantly impact the overall efficacy of the ADC, highlighting the critical importance of maintaining the integrity and compatibility of each element. Alfa Cytology has many years of experience in ADC development, providing customers with the identification and validation of new antigens/antibodies, the development of new payloads with optimal toxicity, and the design of new linkers that balance the stability and payload release. Please contact us for more information.
Reference
- Fu, Z., Li, S., Han, S., Shi, C., & Zhang, Y. (2022). Antibody drug conjugate: the "biological missile" for targeted cancer therapy. Signal transduction and targeted therapy, 7(1), 93. https://doi.org/10.1038/s41392-022-00947-7
! For research use only.
Related Services
