Special Report on Antibody-Drug Conjugates: Technical Challenges and Opportunities

Angelo DePalma

November 14, 2016

1 Min Read

Among the emerging targeted therapies in biotechnology, antibody–drug conjugates (ADCs) hold a unique position. An ADC consists of a monoclonal antibody (MAb) with affinity to tumor cells, a cytotoxic small-molecule payload, and a linker connecting the two. Together the MAb, conjugation chemistry, and cytotoxin increase the complexity of ADCs several-fold relative to unmodified MAbs — and exponentially relative to chemotherapies.

Viewing ADCs as hybrids of antibody- and chemotherapy-based cancer therapies is tempting. That description applies chemically and structurally, but ADCs’ differences from conventional therapies are striking, as is there underlying rationale. Tiffani A. Manolis (pharma segment manager at Agilent Technologies in Santa Clara, CA) likens ADCs to biosimilars in this way: Developers of the latter use innovator MAbs as comparator molecules, whereas ADCs apply them as delivery vehicles. Same molecule, different strategy — and both rely heavily on analytics for characterization.

ADCs use their antibody components to home in on tumor cells bearing specific markers or receptors. Once bound to those cells, ADC and receptor internalize together, and the small-molecule component releases to kill them. The development pipeline includes several variations on this theme.

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