Abstract

Designing and engineering next generation Antibody Drug Conjugates (ADCs) which has tripartite composition-a biogenic having simple three building blocks in the form of monoclonal antibody (mAb), the toxin warhead (payload) and linker, often comes with intrinsic intricacies, has huge scope and potential. Antibody scaffold (mostly of the IgG class), is the main architecture of ADCs that provides firm grip that holds the payload. Structural characteristics of the antibody moiety of ADCs play a pivotal role in functionality of ADCs. Clinically successful ADCs will come with the premise of selecting an appropriate scaffold and tweaking them, has been routinely applied to upgrade the pharmacokinetic (PK) properties. The next generation ADCs will come into reality with delicate and rationale engineering of ADC incorporating aesthetics of science and arts. Development of pro drugs (Active Pharmaceutical Ingredients: APIs) by antibody engineering (for example: glyco-engineering) based on grounds of structural characteristics will facilitate the desired results, thereby achieving variable DARs (drug to antibody ratio) and refinement of the pharmacokinetics by exhibiting relatively low clearance, optimum tissue penetration (bio availability) and longer half-lives with minimized off-target toxicities. Overall these parameters affect the functional attributes (efficacy and potency) of ADCs.