Table 1.
Peptides targeting immune checkpoint molecules.
| Mechanism of action |
Peptide name |
Sequence | Discovery method | Cancer model | Administration method |
Modifications for improving stability |
Ref |
|---|---|---|---|---|---|---|---|
| PD-L1 inhibitor | AUNP-12 | SNTSESFK(SNTSESF)FRVTQLAPKAQIKE | Crystal structure analysis | B16F10 melanoma, Renca renal cell carcinoma, CT26 colon cancer | Subcutaneous | [15,24] | |
| PD-L1 inhibitor | Peptide-57 | Cyclic[F-NMeA-NPHLSWSW-NMeNle-NMeNle-R-Scc]G | N/A | N/A | Cyclic structure, incorporation of unnatural amino acids | [25-27] | |
| PD-L1 inhibitor | Peptide-71 | Cyclic[F-NMeF-NMeNle-Sar-DV-NMeF-Y-Sar-WYL-Scc]G | N/A | N/A | Cyclic structure, incorporation of unnatural amino acids | [25-27] | |
| PD-L1 inhibitor | Peptide-99 | Cyclic[FLIVIRDRVFR-Scc]G | N/A | N/A | Cyclic structure, incorporation of unnatural amino acids | [25-27] | |
| PD-L1 inhibitor | IMB-P6-10 | LTCSLAPNIISAL | Derivative of PRDX5 | C16 colon cancer, CT26 colon cancer | Intraperitoneal | [34] | |
| PD-L1 inhibitor | CLP002 | WHRSYYTWNLNT | Screening by phage display | CT26 colon cancer | Intraperitoneal | [35] | |
| PD-L1 inhibitor | TPP-1 | SGQYASYHCWCWRDPGRSGGSK | Screening by bacterial surface display | H460-luc non-small cell lung cancer | Subcutaneous | [36,37] | |
| PD-L1 inhibitor | DPPA-1 | NYSKPTDRQYHF ※ All amino acids are D-enantiomer |
Screening by mirror image phage display | CT26 colon cancer | Subcutaneous, intraperitoneal | (D)-enantiomeric structure | [38] |
| PD-L1 inhibitor | PD-L1Pep-1 | CLQKTPKQC | Screening by phage display | CT26 colon cancer | Intravenous | [44] | |
| PD-L1 inhibitor | PD-L1Pep-2 | CVRARTR | Screening by phage display | CT26 colon cancer | Intravenous | [44] | |
| Binds to PD-L1 | WL12 | Cyclic[AcY-NMeA-NPHL-Hyp-WS-MeW-NMeNle-NMeNle-Orn-C]G | N/A | N/A | Cyclic structure, incorporation of unnatural amino acids | [28] | |
| Binds to PD-L1 | RK-10 | GSGSGSTYLCGAISLAPKAQIKESL | Crystal structure analysis | N/A | [50] | ||
| Binds to PD-L1 | SPAM | MPIFLDHILNKFWILHYA | Screening by mRNA display | N/A | [51] | ||
| PD-L1 degradation by lysosome | PD-LYSO | DKEMAATSAAIEDAVRRIEDMMNQYPYDVPDYAMDFSGLSLIKLKKQOH | Derivative of HIP1R | In vitro only | [45] | ||
| PD-1 inhibitor | Ar5Y_4 | GNWDYNSQRAQLYNQ | Crystal structure analysis | In vitro only | [29] | ||
| PD-1 inhibitor | PL120131 | Ac-GADYKRITVKVN | PD-L1 derivative | In vitro and 3D culture model only | [30] | ||
| PD-1 inhibitor | YT-16 | Cyclic[YRCMISYGGADYKCIT] | Virtual screening | In vitro only | Cyclic structure | [31] | |
| Binds to PD-1 | WANG | WANG-003: KRWWR WANG-004: FRWWR WANG-005: RRWQWR | Virtual screening | N/A | [49] | ||
| CTLA-4 inhibitor | ERY2-4 | CAWGQAILEGELAWLEGGGGGAGQLADLKRQLAWWKQAC | Screening by yeast surface display | In vitro only | [46] | ||
| TIGIT inhibitor | DTBP-3 | GGYTFHWHRLNP ※ All amino acids are D-enantiomer |
Screening by mirror image phage display | CT26 colon cancer, B16-OVA melanoma, 4 T1 breast cancer | Subcutaneous, intraperitoneal | (D)-enantiomeric structure | [42] |
| LAG-3 inhibitor | C25 | Cyclic[CVPMTYRAC] | Screening by phage display | CT26 colon cancer, B16 melanoma | Subcutaneous | Cyclic structure | [47] |
| Binds to BTLA | HVEM (23–39) | Ac-YRVKEACGELTGTVCEP | Derivative of HVEM | N/A | [52] |
NMeA: N-methylalanine, NMeNle: N-methylnorleucine, Scc: S-Carbamoylcysteine, NMeF: N-methylphenylalanine, Sar: Sarcosine, AcY: Acetyltyrosine, Hyp: Hydroxyproline, MeW: Methyltryptophan, Orn: Ornithine.