A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis

摘要: FS102 is a HER2-specific Fcab (Fc fragment with antigen binding), which binds HER2 high affinity and recognizes an epitope that does not overlap those of trastuzumab or pertuzumab. In tumor cells express levels HER2, caused profound internalization degradation leading to cell apoptosis. The antitumor effect in patient-derived xenografts (PDXs) correlated strongly the amplification status tumors. Superior activity over combination pertuzumab was observed vitro vivo when gene copy number equal exceeded 10 per based on quantitative polymerase chain reaction (qPCR). Thus, induced complete sustained regression significant proportion HER2-high PDX models. We hypothesize unique structure and/or enables internalize degrade surface more efficiently than standard care antibodies. turn, increased depletion commits apoptosis as result oncogene shock. has potential biomarker-driven therapeutic derives superior effects from mechanism-of-action are oncogenically addicted pathway due overexpression.