Table 1.
Pancreatic cancer associated antigens in ADC pre-clinical development
| 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 | [40, 41] |
| 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) |
[55–57] |
| 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] |
ADC: antibody drug conjugate; CEA: carcinoembryonic antigen; DR5: death receptor 5; EGFR: epidermal growth factor receptor; GPC-1: glypican-1; HER3: human epidermal growth factor receptor 3; ICAM-1: intracellular adhesion molecule 1; MMAE: monomethyl auristatin E; MMAF: monomethyl auristatin F; MUC1: mucin-1; SMCC: succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate; Trop2: trophoblast antigen 2; VC: valine-citrulline