Antibody-Drug Conjugate
Antibody-drug conjugates (ADCs) are an important class of highly potent biopharmaceutical drugs, which are created by coupling a small molecule anticancer drug or a therapeutic agent to an antibody that specifically targets a certain tumor marker. Through combining the targeting capabilities of monoclonal antibodies with the cancer-killing ability of cytotoxic drugs, ADCs are able to distinguish between healthy and diseased tissue. Therefore, ADCs are intended to target and kill only the cancer cells but not healthy cells compared with traditional chemotherapy drugs. ADCs have been designed as a targeted therapy for the treatment of cancer and have drawn wide attention among the public.
For ADCs, antibodies targeting a specific antigen are only found on target cells. Once it binds to the cell, it triggers internalization of the antibody, together with the drug. This delivers drugs with a very high specificity to the diseased cells, in turn, leading to cell death. It maximizes the efficacy and minimizes systemic exposure to the associated risk of side effects.
BOC Sciences has studied and developed ADCs over a decade and possesses rich experience in antibody engineering, synthetic chemistry, and bio-conjugation. We are a leader in the field of antibody-drug conjugate research and development, and backed by a highly experienced team, which enables us to offer a comprehensive ADCs development services, and to help create highly customized ADCs. The physicochemical attributes of monoclonal antibody can be fully characterized as follows:
Purity
It is a regulatory requirement that the data that confirms the identity and the purity of your biopharmaceutical should be provided. The product purity of ADC can be characterized by applying a range of analytical approaches, including SDS-PAGE/capillary gel electrophoresis, size-exclusion chromatography and other charge-variant assays. SDS-PAGE/capillary gel electrophoresis is perhaps the most common methodology.
Drug Antibody Ratio
Conjugation of the monoclonal antibody and toxin typically generates a mixture ADCs with varied drug-to-antibody ratios (DAR). DAR describes the degree addition that has direct effect on both potency and potential toxicity of the therapeutic, and has significant effects on properties such as stability and aggregation. Therefore, the determination of DAR is critical for the development of effective ADC. Hydrophobic interaction chromatography (HIC) with UV detection is an excellent means of determining these characteristics.
Stability
The stability profile of an ADC includes physical stability, chemical stability and in vitro / in vivo plasma stability. ADC stability is an important factor in ADC formulation and development which has profound impact on the safety and therapeutic efficacy of an ADC. Before a newly generated ADC is applied in animal or human systems, its stability must be validated. ADC stability assessment is performed via chromatographic and electrophoretic methods. Typically the analytical method applied to the mAb can be applied or adapted to the ADC.
BOC Sciences has years of experience in ADC design, production and analysis, and is working to meet your unique needs in ADCs development projects. Please contact us for more detailed information on ADCs.
Reference
Beverly A. Teicher and Ravi V. J.Chari (2011) ‘Antibody conjugate therapeutics: challenges and potential’. Clinical cancer research, 17(20): 6389-6397.