4.4 Review

Antibody drug conjugates

Journal

BIOTECHNOLOGY LETTERS
Volume 38, Issue 10, Pages 1655-1664

Publisher

SPRINGER
DOI: 10.1007/s10529-016-2160-x

Keywords

Brentuximab vedotin; Chemical linkers; Conjugation; Cytotoxicity; Payload; Solid tumors; Transtuzumab emtansine

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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 (http://www.clinicaltrials.gov) using the keyword 'antibody drug conjugate', yielded similar to 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.

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