Antibody drug conjugates
Antibody drug conjugates (ADCs) have emerged as a viable option in targeted delivery of highly potent cytotoxic drugs in treatment of solid tumors. At the time of writing, only two ADCs have received regulatory approval with >40 others in clinical development. The first generation ADCs suffered from a lack of specificity in amino acid site conjugations, yielding statistically heterogeneous stoichiometric ratios of drug molecules per antibody molecule. For the second generation ADCs, however, site specific amino acid conjugation using enzymatic ligation, introduction of unnatural amino acids, and site specific protein engineering hold promise to alleviate some of the current technical limitations. The rapid progress in technology platforms and antibody engineering has introduced novel linkers, site specific conjugation chemistry, and new payload candidates that could possibly be exploited in the context of ADCs. A search using the Clinical Trial Database registry (www.clinicaltrials.gov) using the keyword 'antibody drug conjugate' yielded ~270 hits. The main focus of this article is to present a brief overview of the recent developments and current challenges related to ADC development.
Biotechnology Letters