For a long time, chemotherapy has been one of the main treatment options for cancer treatment. However, due to its poor specificity for tumor cells/tissues, chemotherapy is usually associated with a lower treatment window. The antibody-drug conjugate (ADC) technology may provide a potential new therapeutic solution for cancer treatment.

Antibody-drug Conjugate (ADC) refers to an antibody connected to a small molecule payload with a cell-killing effect through a chemical linker. After encountering a tumor cell, the ADC will bind to the protein on the surface of the tumor cell. Through chemical, enzymatic, or biological processes, the ADC linker is torn apart and releases a small molecule payload, which then kills tumor cells. This therapy is conceived to deliver cancer-killing drugs specifically to cancer cells like a missile, while protecting healthy cells from harm.

ADC is a complex entity that combines the characteristics of biological drugs and chemical drugs. It needs to be considered from a system perspective, and the overall effect should be improved on the basis of an in-depth understanding of the ADC molecular structure-function relationship in order to obtain the best therapeutic effect. The production of ADC drugs needs to meet the following four requirements:
(1)The choice of antibody: The antibody needs to be directed against tumor-specific (related) antigens, with high expression levels, good endocytosis efficiency, good antigen affinity, no immunogenicity, and drug accessibility.
(2)The choice of linker: It needs to be stable in the blood circulation, disintegrate quickly in the cell, and release poisons efficiently.
(3)Connection method: It should be fixed-point coupling and can produce uniform antibody conjugates.
(4)Payload: Generally, the toxin is required to be sufficiently toxic, with an IC50 value of 0.01-0.1nM; sufficient water solubility and stability in serum; the target of the poison is located in the cell.

As a promising new type of biotechnology drug for cancer cells, the development of Antibody-drug Conjugate (ADC) is carried out worldwide. At present, 13 ADC drugs have been on the market, and they have shown good sales growth in all regions. The indications of these ADC drugs are concentrated in the field of oncology. Of the 13 drugs on the market, 6 drugs target solid tumors (breast cancer, bladder cancer, gastric cancer, etc.) and 7 drugs target hematomas.

According to the analysis of the researchers, the chemical connection method of the antibody and the drug, the number of drugs on the antibody, the stability of the chemical linker, and whether the payload is suitable for a specific tumor type are the key research directions of ADC drug development.

However, the complex structure of ADC and its high degree of heterogeneity pose a huge challenge to its structural characterization. Among them, the determination of drug-to-antibody ratio (DAR), drug coupling site, and site coupling ratio is quite complicated and difficult. BOC Sciences, a well-known antibody-drug conjugate (ADC) drug development solution provider, claims that its its unique and comprehensive modification and coupling solutions can solve these problems.

The antibody modification and coupling strategies offered by BOC Sciences include the following:
Cysteine conjugate
Cysteine coupling provides a flexible choice for the production of non-specific and specific site ADCs. The traditional cysteine coupling is easy to perform, without the need to recombine antibodies or change the cell culture environment to introduce coupling groups. This strategy is applicable to Fab and full-length IgG.
Lysine-based binding
Lysine binding is the most common non-specific coupling method. A large number of lysine residue sites can be used for modification in IgG scaffolds. BOC Sciences can perform lysine conjugation in antibody-drug conjugate (ADC) development.
Carbohydrate conjugate
BOC Sciences has developed various bioconjugation strategies through the carbohydrate portion of the antibody. Carbohydrate combination is an effective method for the development of site-specific ADCs. It is suitable for binding to glycosylated full-length IgG without the need for antibody protein sequence modification or engineering.
Unnatural amino acids conjugation
BOC Sciences can use unnatural amino acids with orthogonal chemical reactivity with standard amino acids to synthesize site-specific antibody-drug conjugates (ADC), and introduce unnatural amino acid residues into the antibody by biological means to improve drugs Specificity of coupling.
Other Conjugation Approaches
With expertise in the production of antibody drug conjugates (ADC), BOC Sciences also provides other coupling methods, including enzymatic modification of antibodies. Enzymatically modified antibodies can be used for site-specific coupling. In this method, enzymes that recognize specific amino acid tags are developed for site-specific antibody coupling.

In addition to antibody modification and conjugation strategies, ADC payloads, ADC linkers and ADC cytotoxin are available at BOC Sciences. Besides, this company's advanced laboratory analytical instruments can perform comprehensive characterization and purity determination of ADC products.