Antibody-drug Conjugates Based on SPR Technology

The overview of antibody-drug conjugates

Antibody-drug conjugates are a new class of drugs that chemically link monoclonal antibodies to drugs that can kill cancer cells. Monoclonal antibodies by themselves are often not sufficiently cytotoxic in the field of cancer therapy. However, small molecule anticancer drugs lack the selectivity of target cells, and they are easy to cause systemic toxicity in patients when used alone. Antibody-drug conjugates can combine the advantages of the two components to a great extent and reduce the disadvantages when used alone. Different from traditional chemotherapeutic drugs, antibody-conjugated drugs are a new type of targeted cancer therapy drugs, which can specifically introduce drugs into targeted sites and kill target cancer cells without affecting the function of healthy cells. Therefore, the antibody-drug conjugate can achieve a significant therapeutic effect with high selectivity and low side effects. Antibody-drug conjugates generally organically combine antibodies and cytotoxic drugs through a stable linker, which can simultaneously enhance the specific recognition of antibodies to target antigens and the high efficiency of cytotoxic drugs. In fact, the selection of antibodies, linkers, coupling methods, and drug-antibody binding ratio (DAR) may all affect the binding of antibody-drug conjugates to target molecules. Among them, antibody backbone molecules generally need to have the characteristics of specific target recognition, high affinity, and long half-life at the same time, in order to be expected to become cytotoxic drug delivery carriers. The ideal antibody needs to have a high affinity with the target molecule, and the general KD is pM~nM. This requires that in the design and development of antibody-drug conjugates, researchers need to choose a technology with high sensitivity, good specificity, and a wide range of affinity detection to conduct comprehensive detection and analysis of the physicochemical properties of antibody-drug conjugates.

Figure.1 Structure of an antibody drug conjugate and properties of the antibody, linker, and cytotoxic payload components (Chau, C, H, et al., 2019)

Surface plasmon resonance (SPR) in the process of antibody-drug conjugates research

Based on the obvious therapeutic advantages of antibody-drug conjugates compared with antibody drugs and small molecule drugs, antibody-drug conjugates have excellent development potential and prospects. As also mentioned above, the interaction analysis between antigen-antibody and toxin molecules is an important part of the development process of antibody-drug conjugates. If you need a high-sensitivity, high-specificity and high-throughput intermolecular affinity analysis assistant, you can try our SPR technology platform. We can provide you with high-throughput antigen-antibody affinity analysis services and rich molecular interaction data after a single run. Specifically, several types of services that can be provided in the R&D stage of antibody conjugated drugs are as follows.

Fig.2 BIAchip^TM in the process of antibody-drug conjugates research

• Binding activity detection and consistency evaluation service of antibody conjugated drug and target

The SPR technology platform can screen candidate antibody-drug conjugates through high-throughput analysis of the binding of antibody-drug conjugates to targets. Based on the high sensitivity of SPR technology platform, it has extremely high resolution and can accurately characterize the subtle differences of molecules with similar affinity, thereby facilitating the precise screening of different antibody-conjugated molecules.

• Evaluation service of the impact of different Linker designs on the binding activity of antibody-drug conjugates to the target

In the design process of antibody-drug conjugates, different linkers can be selected to couple the antibody and toxin molecules together. There are many designs of linker types and chain lengths. Some linkers can be cleaved from the antibody by enzymatic or acid hydrolysis, while others cannot be cleaved at all. In addition, different linkers couple the antibody to the toxin molecule, which may affect the binding of the antibody to the target. Our SPR technology platform can provide high-throughput and high-sensitivity linker screening services, which can help you accurately determine the impact of these different linkers on the binding activity of antibody-drug conjugates to the target.

• Service for evaluating the effect of DAR on the binding activity of antibody-drug conjugates to the target

The drug-antibody ratio (DAR) is used to determine how many toxin molecules can be conjugated to the antibody during the conjugation process of the antibody-conjugated drug. Different coupling methods can produce different DAR. DAR determines the efficacy of antibody conjugated drugs to a certain extent. Theoretically, if the DAR is larger, the higher the number of toxin molecules carried by the unit antibody, and the higher the number of toxin molecules entering the target cell. Ultimately, the killing effect of the antibody-conjugated drug will be better. However, too high DAR often affects the binding of antibody to target, so it is necessary to detect the effect of different DAR on the binding activity of target in the development of antibody-drug conjugates. Our SPR technology platform can provide you with reproducible high-throughput interaction analysis services to screen out the most suitable DAR for your subsequent development of antibody-drug conjugates.

If you do not find a suitable one for your experimental project in the above services, please feel free to contact us for exclusive customized services. All services from Creative Proteomics are available on a 24/7/365 basis.

For research use only. Not intended for any clinical use.