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• W2890358541 abstract "Abstract Cancer-induced blood coagulation in human tumour generates insoluble fibrin (IF)-rich cancer stroma in which uneven monoclonal antibody (mAb) distribution reduce the potential effectiveness of mAb-mediated treatments. Previously, we developed a mAb that reacts only with IF and not with fibrinogen (FNG) or the fibrin degradation product (FDP). Although IF, FNG and FDP share same amino acid sequences, the mAb is hardly neutralised by FNG and FDP in circulation and accumulates in fibrin clots within tumour tissue. Here, we created an antibody drug conjugate (ADC) using the anti-IF mAb conjugated with a chemotherapy payload (IF-ADC). The conjugate contains a linker severed specifically by plasmin (PLM), which is activated only on binding to IF. Imaging mass spectrometry showed the substantial intratumour distribution of the payload following the IF-ADC injection into mice bearing IF-rich 5–11 xenografts derived from pancreatic tumours of LSL-Kras G12D/+ ; LSL-Trp53 R172H/+ ; Ptf1a-Cre (KPC) mice. IF-ADC treatment significantly extended the survival of the KPC mice. These data suggest that conjugating chemotherapy drugs to this IF-specific mAb could represent an effective means of treating stroma-rich tumours" @default.
• W2890358541 created "2018-09-27" @default.
• W2890358541 creator A5021197136 @default.
• W2890358541 creator A5028273614 @default.
• W2890358541 creator A5051774299 @default.
• W2890358541 creator A5079871502 @default.
• W2890358541 date "2018-09-21" @default.
• W2890358541 modified "2023-10-14" @default.
• W2890358541 title "Chemotherapy payload of anti-insoluble fibrin antibody-drug conjugate is released specifically upon binding to fibrin" @default.
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• W2890358541 doi "https://doi.org/10.1038/s41598-018-32601-0" @default.
• W2890358541 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6155080" @default.
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• W2890358541 hasPublicationYear "2018" @default.
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