Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes
Abstract
:Simple Summary
Abstract
1. Introduction
2. NK Cells
2.1. PD-1
2.2. KIRs
2.3. NKG2A
2.4. TIM-3
2.5. TIGIT
2.6. LAG-3
3. Helper ILCs
3.1. PD-1
3.2. PD-1 Expression on ILCs in Cancer
3.3. CTLA-4
3.4. TIGIT and CD96, and TGF-β
3.5. KLRG1
3.6. TIM-3
3.7. LAG-3
3.8. NKG2A
3.9. Metabolic Checkpoints
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Receptor | Cell Type | mAbs Used in Clinical Trial | Tissue/Tumor Involvement | Clinical Trial Number/Phase | Recruitment Information |
---|---|---|---|---|---|
PD-1 | NK | Several anti-PD-1 mAbs, reviewed in [25] | Solid tumors, including Kaposi sarcoma, PC, ovarian and lung cancers [26,27,28,29,30], and HL [31] | ||
Use of anti-PD-1 or anti-PD-L1 improves the anti-tumor activity of NK cells against PD-L1/2+ tumor cells [25,26,31,32] | |||||
ILC | Decidual ILCs during pregnancy [17] | ||||
Tumor-associated ILC2s (>PD-1 than circulating ILCs) [33] | |||||
ILC2s and ILC3s in tumors of the gastrointestinal tract (>PD-1 than in the paralesional tissue) | |||||
ILC3s in human malignant pleural effusion [30] | |||||
ILC2s in colorectal cancer model [33] | |||||
KIRs | NK | Monotherapy with IPH2102 (lirilumab) | Solid tumors, hematologic malignancies, all pediatric tumor types [34] | ||
IPH2102 combined with anti-PD-1 (nivolumab) | Bladder cancer | NCT03532451 phase 1 | 43 participants (active) | ||
SCCHN | NCT03341936 phase 2 | 58 participants (active/recruiting) | |||
Advanced solid tumors | NCT03203876 phase 1 | 21 participants (active) | |||
Leukemia | NCT02599649 phase 2 | 10 participants (terminated/results) | |||
HL, NHL, MM | NCT01592370 Phase 1/2 | 375 participants (active) | |||
IPH2102 combined with anti-PD-1 (nivolumab)+ anti-CTLA-4 (ipilimumab) | Advanced solid tumors | NCT01714739 Phase 1/2 | 337 participants (completed) | ||
Advanced solid tumors | NCT03347123 Phase 1/2 | 11 participants (active) | |||
IPH2102 combined with anti-CS1 (elotuzumab) | MM | NCT02252263 Phase 1 | 44 participants (completed) | ||
IPH2102 combined with anti-CD20 (rituximab) | CLL | NCT02481297 phase 2 | 7 participants (completed/results) | ||
Monotherapy with 1-7F9 | MM | NCT00552396 phase 1 | 32 participants (completed/results) | ||
IPH2102 combined with azacytidine | AML | NCT02399917 phase 2 | 36 participants (terminated/results) | ||
MDS | NCT02599649 phase 2 | 10 participants (terminated/results) | |||
NKG2A | NK | Monotherapy with IPH2201 (monalizumab) [35] | Gynecologic cancers | NCT02459301 phase 1 | 59 participants (completed) |
IPH2201 combined with anti-PD-L1 (durvalumab) [36] | NSCLC | NCT03822351 phase 2 | 189 participants (active) | ||
NSCLC | NCT03833440 phase2 | 120 participants (recruiting) | |||
NSCLC | NCT03794544 phase 2 | 80 participants (active) | |||
MSS-CRC | NCT04145193 phase 2 | Withdrawn | |||
Advanced solid tumors | NCT02671435 phase 1/2 | 383 participants (active) | |||
IPH2201 combined with anti-EGFR (cetuximab) or with anti-EGFR +anti-PD-L1 | SCCHN | NCT02643550 phase 1/2 | 140 participants (recruiting) | ||
IPH2201 combined with anti-Bruton’s tyrosine kinase (ibrutinib) | CLL | NCT02557516 phase 1/2 | 22 participants (terminated/results) | ||
ILC | AML [37] | ||||
TIM-3 | NK | Gastric cancer [38] Lung adenocarcinoma [39] Advanced melanoma [40] Bladder cancer [38,39,40,41] | |||
Sym023 | Metastatic cancer, solid tumor, lymphomas | NCT03489343 phase 1 | 24 participants (completed) | ||
Sym023 combined with anti-PD-1 or anti-LAG-3 | NCT03311412 phase 1 | 102 participants (recruiting) | |||
TSR-022 combine with anti-PD-1 | Advanced solid tumors | NCT02817633 phase 1 | 369 participants (recruiting) | ||
TSR-022 combine with anti-PD-1 | NCT04139902 phase 2 | 56 participants (recruiting) | |||
TSR-022 combine with anti-PD-1 | Primary liver cancer | NCT03680508 phase 2 | 42 participants (recruiting) | ||
BMS-986016 (relatlimab) combined with anti-PD-1 (nivolumab) | Chordoma | NCT03623854 phase 2 | 20 participants (recruiting) | ||
Metastatic uveal melanoma | NCT04552223 phase 2 | 27 participants (recruiting) | |||
Melanoma | NCT03743766 phase 2 | 42 participants (recruiting) | |||
BGB-A425 combined with anti-PD-1 | Advanced or metastatic solid tumors | NCT03744468 phase 1/2 | 162 participants (recruiting) | ||
Monotherapy with MBG453 | Advanced malignancies | NCT02608268 phase 1/2 | 252 participants (active) | ||
AML or high risk MDS | NCT03066648 phase 1 | 235 participants (recruiting) | |||
ILC | TIM-3+ ILC3s were found in the decidua [17] | ||||
TIGIT | NK | Colon cancer patients and tumor models [42] | |||
TIGIT blocking was suggested as a potent strategy to increase graft versus leukemia effect in alloSCT in AML [43] | |||||
Tiragolumab combined with anti-PD-1 (atezolizumab) | Cervical cancer | NCT04300647 phase 2 | 160 participants (recruiting) | ||
Esophageal squamous cell carcinoma | NCT04543617 phase 3 | 750 participants (recruiting) | |||
SCLC | NCT04256421 phase 3 | 400 participants (recruiting) | |||
NSCLC | NCT04513925 phase 3 | 800 participants (recruiting) | |||
NCT03563716 phase 2 | 135 participants (active) | ||||
Esophageal Cancer | NCT04540211 phase 3 | 450 participants (recruiting) | |||
NCT03281369 phase 1/2 | 410 participants (recruiting) | ||||
Urothelial carcinoma | NCT03869190 phase 1/2 | 385 participants (recruiting) | |||
Pancreatic adenocarcinoma | NCT03193190 phase 1/2 | 290 participants (recruiting) | |||
Advanced metastatic tumors | NCT02794571 phase 1 | 400 participants (recruiting) | |||
Tiragolumab combined with anti-VEGF (bevacizumab) | Advanced liver cancer | NCT04524871 phase 1/2 | 100 participants (recruiting) | ||
Monotherapy with BMS-986207 or combined with anti-LAG-3 | MM | NCT04150965 phase 1/2 | 104 participants (recruiting) | ||
BMS-986207 combined with nivolumab | Ovarian cancer, endometrial neoplasmas, solid tumor | NCT04570839 phase 1/2 | 100 participants (recruiting) | ||
Monotherapy with OMP-313M32 or combined with anti-PD-1 (nivolumab) | Advanced and metastatic cancer | NCT03119428 phase 1 | 33 participants (terminated) | ||
Monotherapy with AB154 or combined with anti-PD-1 (zimberelimab) | Advanced solid tumors | NCT03628677 phase 1 | 66 participants (recruiting) | ||
Lung cancer | NCT04262856 phase 2 | 150 participants (recruiting) | |||
ILC | ILC1 and splenic ILC3 [44] | ||||
LAG-3 | NNK | Monotherapy with Sym022 | Metastatic cancer, solid tumor, and lymphoma | NCT03489369 phase 1 | 15 participants (completed) |
Monotherapy with BMS-986016 (relatlimab) or combined with anti-PD-1 | Brain neoplasms, glioblastoma, gliosarcoma | NCT02658981 phase 1 | 63 participants (active) | ||
Solid tumors | NCT01968109 phase 1/2 | 1500 participants (recruiting) | |||
NCT03470922 phase 2/3 | 700 participants (recruiting) | ||||
SCCHN | NCT04080804 phase 2 | 60 participants (recruiting) | |||
MK-4280 combined with anti-PD-1 | Solid tumors | NCT02720068 phase 1 | 576 participants (recruiting) | ||
Hematologic malignancies | NCT03598608 phase 1/2 | 134 participants (recruiting) | |||
Monotherapy with TSR-033 or combined with anti-PD-1 | Advanced solid tumors | NCT03250832 phase 1 | 55 participants (recruiting) | ||
Monotherapy with LAG525 or combined with anti-PD-1 | Advanced solid tumors | NCT02460224 phase 1/2 | 490 participants (active) | ||
NCT03499899 phase 2 | 88 participants (active) | ||||
NCT03484923 phase 2 | 195 participants (recruiting) | ||||
Solid and hematologic malignancies | NCT03365791 phase 2 | 76 participants (completed) | |||
Monotherapy with REGN3767 or combined with anti-PD-1 | Advanced malignancies | NCT03005782 phase 1 | 669 participants (recruiting) | ||
Monotherapy with IMP321 (eftilagimod alpha) or combined with chemotherapy | Melanoma [45] | NCT02676869 phase 1 | 24 participants (completed) | ||
Metastatic breast cancer | NCT00349934 phase 1 | 33 participants (completed) | |||
IMP321 (eftilagimod alpha) combined with anti-PD-1 | NSCLC and SCCHN | NCT03625323 phase 2 | 109 participants (recruiting) | ||
ILC | LAG-3 upregulated upon tumor conversion from NKs to ILC1s [46] | ||||
KLRG1 | ILC | KLRG1 protein expressed from ILC3s isolated from first trimester decidual tissue [17] and in a subset of ILC2s in vivo expanded with IL-25 [47] | |||
KLRG1 transcripts identified in ILC2s in lung and colorectal cancer [20] | |||||
CTLA-4 | ILC | Expression of CTLA-4 in tumor associated ILC1s and ILC2s [33,46] |
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Pesce, S.; Trabanelli, S.; Di Vito, C.; Greppi, M.; Obino, V.; Guolo, F.; Minetto, P.; Bozzo, M.; Calvi, M.; Zaghi, E.; et al. Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes. Cancers 2020, 12, 3504. https://doi.org/10.3390/cancers12123504
Pesce S, Trabanelli S, Di Vito C, Greppi M, Obino V, Guolo F, Minetto P, Bozzo M, Calvi M, Zaghi E, et al. Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes. Cancers. 2020; 12(12):3504. https://doi.org/10.3390/cancers12123504
Chicago/Turabian StylePesce, Silvia, Sara Trabanelli, Clara Di Vito, Marco Greppi, Valentina Obino, Fabio Guolo, Paola Minetto, Matteo Bozzo, Michela Calvi, Elisa Zaghi, and et al. 2020. "Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes" Cancers 12, no. 12: 3504. https://doi.org/10.3390/cancers12123504