May 2019 Featured Report

An antibody–drug conjugate (ADC) for cancer treatment needs four things to succeed clinically: It needs to target the right antigen using the right antibody, with the most powerful cytotoxin attached by best linker option. These features combine to endow the resulting conjugated product with therapeutic safety and efficacy. Figure 1: Three parts of an antibody–drug conjugate Antigens: Determining which receptor to target is the first step in ADC development. The best options are expressed highly and consistently on the surface of a number of tumor cell types — but absent from normal tissues (or at least expressed at very low levels) — and won’t be downregulated after initial ADC treatment. If tumor cells stop expressing that antigen in reaction to their first exposure to a drug, then subsequent treatments won’t have the same cytotoxic effect. Tumor-specific antigens are the ideal choice, although so far most ADCs have targeted antigens that are only tumor “associated” (e.g., HER2 in breast cancer). Anti...