Table 1 Pancreatic cancer associated antigens in ADC pre-clinical development
From: Antibody drug conjugates: hitting the mark in pancreatic cancer?
Target Antigen | ADC name | Linker | Payload | Pre-clinical model | Reference |
|---|---|---|---|---|---|
EGFR | RN765C | Cleavable VC | PF-06380101 (microtubule inhibitor) | BxPC3 pancreatic xenograft | [32] |
RC68 | Cleavable VC | MMAE (auristatin) | BxPC3 pancreatic xenograft | [33] | |
CTX-MMAE | Cleavable dibromopyridazinedione VC | MMAE (auristatin) | MIA PaCa-2 and PANC-1 pancreatic xenograft | [34] | |
LR004 | Non-cleavable SMCC | DM1 (maytansinoid) | Capan-2 pancreatic xenograft | [35] | |
Mesothelin | BAY 94-9343 (Anetumab Ravtansine) | Cleavable (disulfide) | DM4 (maytansinoid) | MIA PaCa-2 (overexpressing mesothelin) pancreatic xenograft Patient-derived pancreatic model (PAXF736) | [18] |
AMA-MMAE | Cleavable VC | MMAE (auristatin) | Capan-2, HPAC, AsPC-1 and HPAF-II pancreatic xenograft | [36] | |
CEA | Labetuzumab-SN-38 | Cleavable | SN-38 (topoisomerase I inhibitor) | Capan-1 pancreatic xenograft | [37] |
α-CEA-680-PTX | Cleavable (disulfide) | Paclitaxel | BxPC3 pancreatic xenograft | [38] | |
SAR408701 | Cleavable | DM4 (maytansinoid) | N/A | [39] | |
Trop2 | hRS7 | Cleavable | SN-38 (topoisomerase I inhibitor) | Capan-1 and BxPC3 pancreatic xenograft | |
RN927C | Cleavable VC | PF-06380101 (microtubule inhibitor) | BxPC3 pancreatic xenograft Patient-derived pancreatic model (Pan0123, Pan0135, and Pan0146) | [42] | |
Tissue factor | Anti-human ADC and anti-mouse ADC | Cleavable VC | MMAE (auristatin) | Capan-1 and BxPC3 pancreatic xenograft | [43] |
Anti-TF ADC | Cleavable VC | MMAE (auristatin) | TF-expressing murine pancreatic model (mPan) | [44] | |
Anti-TF ADC (humanized) | Cleavable VC | MMAE (auristatin) | BxPC3 and HPAF-II pancreatic xenograft | [45] | |
SC1-DM1 SC1-MMAE | Non-cleavable Cleavable VC | DM1 (maytansinoid) MMAE (auristatin) | BxPC3 pancreatic xenograft | [46] | |
TF-011-MMAE TF-011-MMAF TF-098-MMAE TF-098-MMAF TF-111-MMAE TF-111-MMAF | Cleavable VC Non-cleavable Cleavable VC Non-cleavable Cleavable VC Non-cleavable | MMAE (auristatin) MMAF (auristatin) MMAE (auristatin) MMAF (auristatin) MMAE (auristatin) MMAF (auristatin) | HPAF-II, AsPC-1 and BxPC3 pancreatic xenograft | [47] | |
HER3 | HER3-ADC | Cleavable VC | MMAE (auristatin) | BxPC3 and HPAC pancreatic xenograft and patient-derived pancreatic model (PDX P4604) | [48] |
EV20/NMS-P945 | Cleavable | NMS-P528 (DNA alkylating agent) | BxPC3 pancreatic xenograft | [49] | |
CD70 | SGN-75 | Non-cleavable | MMAF (auristatin) | CD70 transfected MIA PaCa-2 pancreatic xenograft | [50] |
MUC1 | SAR566658 | Cleavable | DM4 (maytansinoid) | Capan-2 pancreatic xenograft | [51] |
HzMUC1-MMAE | Cleavable VC | MMAE (auristatin) | Capan-2 and CFPAC-1 pancreatic xenograft | [52] | |
ICAM1 | ICAM1-DM1 | Non-cleavable SMCC | DM1 (maytansinoid) | PANC-1 pancreatic xenograft | [53] |
CD71 | CX-2029 | Cleavable VC | MMAE (auristatin) | Patient-derived pancreatic model (PA6237) | [54] |
Glypican-1 | GPC1-ADC | Cleavable VC | MMAE (auristatin) MMAF (auristatin) | BxPC3 and BxPC3 GPC-1 Knockout pancreatic xenograft Patient-derived pancreatic model (PK645 PDAC, PK565 PDAC, PK175, and KPK1) | |
SLC44A4 | ASG-5ME | Cleavable VC | MMAE (auristatin) | Patient-derived pancreatic model (AG-Panc3 (orthotopic), AG-Panc4 and AG-Panc2) | [58] |
DR5 | Oba01 | Cleavable VC | MMAE (auristatin) | MIA PaCa-2 and PL45 pancreatic xenograft Patient-derived pancreatic model (PA1266 and PA1198) | [59] |