A Comparative Analysis of Fibroblast Activation Protein-Targeted Small Molecule–Drug, Antibody–Drug, and Peptide–Drug Conjugates

We present the first in vivo comparative evaluation of chemically defined antibody–drug conjugates (ADCs), small molecule–drug conjugates (SMDCs), and peptide–drug conjugates (PDCs) targeting and activated by fibroblast activation protein (FAP) in solid tumors. Both the SMDC (OncoFAP-Gly-Pro-MMAE) and the ADC (7NP2-Gly-Pro-MMAE) candidates delivered high amounts of active payload (i.e., MMAE) selectively at the tumor site, thus producing a potent antitumor activity in a preclinical cancer model.