Linkers help bind antibodies and chemical drugs, which directly affect the ADC pharmacokinetics, therapeutic index and therapeutic effect.
The antibody-binding conjugate must have the following properties: Stability without the release of the cytotoxic drug molecule before it reaches a predetermined target, resulting in non-target toxicity. If the target site is endogenous, drug molecules can be released quickly and efficiently. You can find the immunizer validation service on various sites over the internet.
Image Source: Google
The drug-antibody ratio (DAR) is an important indicator of adjunct choice, in terms of the number of drug molecules that can be transferred per antibody unit. If the antibodies contain too little of the drug, this affects the overall effect. And when the antibody molecules are overloaded, the ADC becomes unstable and changes its pharmacokinetic parameters, which is likely to increase the plasma clearance rate, shorten the half-life and increase the systemic toxicity of the drug.
According to their chemical properties, linkers can be divided into two categories: non-degradable connectors and detachable connectors. In non-degradable adjuncts, the drug remains active after hydrolysis of the lysosome and adheres to amino acid residues in the linking zone, such as T-dm1.
Separate adherents often use different drug-releasing strategies, thus increasing the likelihood of "side effects". Some linkers are sensitive to acidic media and free drug molecules can be released in lysosomes or endocytosis with low pH. Ozogamycin gemtuzumab is characterized by certain plasma instabilities.
Some adjuncts are sensitive to proteases in lysosomes, such as B. Brentuximab vedotin. Others are more sensitive to glutathione and take advantage of high levels of glutathione in tumor cells.