Table 1.
Summary of available targets for natural killer/T cell lymphoma
| Targets | Intervention/treatment | Signal crosslinking | Structure | Prognostic relevance | Percentage of NKTCL with positive expression | Research stage for NKTCL | Reference |
|---|---|---|---|---|---|---|---|
| PD-1 | Pembrolizumab | PD-1/PD-L1, LMP1, MAPK, JAK-STAT and NF-κB | Humanized IgG4 | NA | NA | clinical | Li et al.28 |
| Nivolumab | Humanized IgG4 | clinical | Chan et al.29 | ||||
| Tislelizumab | Humanized IgG4 | clinical | Tao et al.30 | ||||
| Sintilimab | Humanized IgG4 | clinical/preclinical | Yan et al., Wen et al.31,32 | ||||
| Toripalimab | Humanized IgG4 | clinical | |||||
| PD-L1 | Avelumab | PD-1/PDL1, LMP1, MAPK, JAK-STAT and NF-κB | Humanized IgG1 | Disputed | 39%–100% | clinical | Nagato et al., Huang et al., Kim et al., Jo et al., Panjwani et al., Han et al.33,34,35,36,37,38 |
| Sugemalimab | Humanized IgG4 | clinical | |||||
| IMC-001 | Humanized IgG1 | clinical | |||||
| CTLA-4 | Ipilimumab | Humanized IgG1 | NA | clinical | Hosseini et al.39 | ||
| CD25/IL-2Rα | Basiliximab | IL-2, LMP1, MAPK and NF-κB | Murine/human IgG1 | Negative | NA | clinical | Wang et al.40 |
| CD30 | Brentuximab vedotin | NF-κB, MAPKs | Humanized IgG1 | Disputed | 50%–70% | clinical | Kim et al., Zhang et al.41,42 |
| CD38 (TNFRSF8) | Daratumumab | calcium, BCR, TLR | Human IgGκ | Negative | 95% | clinical | Lund, Wang et al., Huang et al., Hari et al., Huang et al.43,44,45,46,47 |
| CD52 | Alemtuzumab | IL-15 | Humanized IgG1 | NA | clinical | Kim et al., Zhang et al.48,49 | |
| CD56 | huN901-DM1 | NA | NA | ∼100% | preclinical | Ishitsuka et al.50 | |
| CCR4 | Mogamulizumab | CCL17/CCR4, CCL22/CCR4 | Humanized IgG1 | NA | 47% | preclinical | Kumai et al., Kanazawa et al.51,52 |
| EBV antigens (LMP1/LMP2) | LMP-CTLs | NA | clinical | ||||
| CAR-T | anti-CD30 CAR-T | NA | clinical | ||||
| anti-CD38 CAR-T | NA | preclinical | Li et al.53 | ||||
| anti-CD7 CAR-T | NA | clinical | |||||
| anti-CD19 CAR-T | NA | clinical |
NKTCL, natural killer/T cell lymphoma; PD-1, programmed death 1; PD-L1, programmed cell death-ligand 1; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; IL-2Rα, IL-2 receptor alpha; EBV, Epstein-Barr virus; CTL, cytotoxic T lymphocyte; LMP1/2, Latent membrane protein 1/2; MAPK, Mitogen-activated protein kinases; JAK-STAT, Janus kinase-signal transducer and activator of transcription; NF-κB, Nuclear factor-κB; CCR4, C-C chemokine receptor 4; CAR-T, Chimeric antigen receptor T-cell; NA, data not available.