An anti-EGFR × cotinine bispecific antibody complexed with cotinine-conjugated duocarmycin inhibits growth of EGFR-positive cancer cells with KRAS mutations

Abstract

Cancer: Improving targeted therapy A new method for producing antibody-drug conjugates (ADCs), pairing anti-cancer drugs with antibodies that deliver them specifically to cancer cells, may help to develop therapies for hard-to-treat cancers. ADCs show promise for treating several cancers, but are difficult to produce. Junho Chung at the Seoul National University College of Medicine in South Korea and co-workers tested a new way of forming the conjugates, using cotinine, a non-toxic molecule related to nicotine, as a link. They bound cotinine to the anti-cancer drug duocarmycin, then formulated an antibody with two binding sites, one for cotinine, one for tumor cells. Combining the drug−cotinine complex with the antibody resulted in a drug–cotinine-antibody ADC that delivered duocarmycin exclusively to cancer cells and inhibited tumor growth in mice. This simplified method may help develop treatments for other drug-resistant cancers.