Immune Checkpoint Blockade: A Strategy to Unleash the Potential of Natural Killer Cells in the Anti-Cancer Therapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. NK Cell Subsets Diversity
3. Expression of MHC Class I- Specific Inhibitory Receptors by NK Cells (Classical ICs)
4. Expression of Non-Classical ICs by NK Cells
5. NK Cell Targeting to Improve Anti-Tumor Response
5.1. Harnessing NK Cells: Immune Checkpoint Inhibitors (ICIs)
5.2. Clinical Data on Therapeutic Approaches in Solid Tumors Involving Both Classical and Emerging/Non-Classical Immune Checkpoints
6. Role of NK Cells in Creating a More Inflamed Environment (to Prepare the Ground for ICI)
7. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Target | Agent | Study | Population | Regimens | Outcomes |
---|---|---|---|---|---|
NKG2A | Monalizumab | Colevas et al. (single-arm phase II trial) [66] | 40 patients with recurrent/advanced SCCHN | Durvalumab plus cetuximab plus monalizumab | ORR: 32.5% Median PFS: 6.9 months; 12 month-OS: 59% |
COAST (open-label, randomized, phase II trial) [67] | 189 patients with stage III NSCLC candidates for maintenance after chemo-radiation | Durvalumab plus monalizumab or durvalumab plus oleclumab vs. durvalumab alone * | Monalizumab + durvalumab arm vs. durvalumab alone Confirmed ORR: 35.5% vs. 17.9% Median PFS: 15.1 vs. 6.3 months | ||
KIR 2D | Lirilumab | Vey et al. (phase I trial) [47] | 37 patients with solid or hematologic malignancies | Escalating doses of lirilumab | No DLT were identified; full KIR occupancy (>95%) was achieved with all dosages |
Armand et al. (phase I trial) [68] | 72 patients with classical Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma | Lirilumab plus nivolumab | ORR: 76% Grade 3–4 TRAE: 15% | ||
Hannah et al. (single-arm phase II trial) [69] | 28 patients with operable SCCHN | Lirilumab plus nivolumab 7–21 days before surgery, followed by 6 cycles of adjuvant lirilumab plus nivolumab | DCR at surgery: 96% 1-year DFS: 55.2% 1-year OS: 85.7% Grade 3+ TRAE: 11% |
Target | Agent | Study | Population | Regimens | Outcomes |
---|---|---|---|---|---|
SLAM7 | Elotuzumab | Yashar et al. (single-arm phase II trial) [76] | 13 patients with high-risk relapsed/refractory multiple myeloma | Elotuzumab plus pomalidomide, carfilzomib, and low-dose dexamethasone | ORR: 45.4%; CBR: 54.5% SAE rate: 31% |
TIGIT | Tiragolumab | CITYSCAPE (open-label, randomized, phase II trial) [70] | 135 patients with advanced NSCLC (PD-L1 ≥ 1%) | Tiragolumab plus atezolizumab vs. atezolizumab alone | INTERIM ANALYSIS * ITT population Median PFS: 5.6 vs. 3.9 months; HR: 0.62 (95% CI: 0.42–0.91) Median OS: 23.2 vs. 14.5 months; HR: 0.69 (95% CI: 0.44–1.07) PD-L1 ≥ 50% Median PFS: 16.6 vs. 4.1 months; HR: 0.29 (95% CI: 0.15–0.53) Median OS: NR vs. 12.8 months; HR: 0.23 (95% CI: 0.10–0.53) PD-L1 between 1–49% Median PFS: 4.0 vs. 3.6 months; HR: 1.07 (95% CI: 0.67–1.71) Median OS: 13.3 vs. 14.5 months; HR: 1.16 (95% CI: 0.70–1.94) |
IDO1 | Epacadostat | ECHO-110 (phase Ib trial) [77] | 29 patients with advanced, pre-treated NSCLC | Epacadostat (increasing doses) plus atezolizumab | Grade ≥ 3 AEs rate: 24% 8 patients achieved stable disease 1 patient achieved partial response |
ECHO-202/KEYNOTE-037 (phase I/II trial) [78] | 62 patients with advanced solid tumors | Epacadostat (increasing doses) plus pembrolizumab | Grade ≥ 3 AEs rate: 24% ORR melanoma: 12/22 patients (55%) ORR NSCLC: 5/12 patients (42%) ORR RCC: 2/11 patients (18%) | ||
ECHO-301/KEYNOTE-252 (placebo-controlled, randomized, phase III trial) [79] | 706 patients with unresectable stage III or IV melanoma previously untreated with PD-1 or PD-L1 checkpoint inhibitors | Epacadostat plus pembrolizumab vs. placebo plus pembrolizumab | Median PFS: 4.7 vs. 4.9 months; HR: 1.00 (95% CI: 0.83–1.21; p = 0.52) Median OS: not reached in any arm; HR: 1.13 (95% CI: 0.86–1.49; p = 0.81) | ||
LAG-3 | Relatlimab | Ascierto et al. (phase I/IIa trial) [72] | 43 patients pre-treated with ICIs for melanoma | Relatlimab plus nivolumab | ORR: 16%; DCR: 45% Any grade AEs rate: 46%; Grade 3–4 AEs rate: 9% |
RELATIVITY-047 (placebo-controlled, randomized, phase II/III trial) [73] | 714 patients with previously untreated advanced melanoma | Relatlimab plus nivolumab vs. placebo plus nivolumab | Median PFS: 10.1 vs. 4.6 months; HR: 0.75 (95% CI: 0.62–0.92; p = 0.006) Grade 3–4 AEs rate: 18.9% vs. 9.7% | ||
TIM-3 | Sabatolimab | Curigliano et al. (phase I/II trial) [75] | 219 patients with solid tumors | Escalating doses of sabatolimab alone or sabatolimab plus spartalizumab | MTD not reached No response with sabatolimab alone ORR (sabatolimab plus spartalizumab): 6% |
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Grottoli, M.; Carrega, P.; Zullo, L.; Dellepiane, C.; Rossi, G.; Parisi, F.; Barletta, G.; Zinoli, L.; Coco, S.; Alama, A.; et al. Immune Checkpoint Blockade: A Strategy to Unleash the Potential of Natural Killer Cells in the Anti-Cancer Therapy. Cancers 2022, 14, 5046. https://doi.org/10.3390/cancers14205046
Grottoli M, Carrega P, Zullo L, Dellepiane C, Rossi G, Parisi F, Barletta G, Zinoli L, Coco S, Alama A, et al. Immune Checkpoint Blockade: A Strategy to Unleash the Potential of Natural Killer Cells in the Anti-Cancer Therapy. Cancers. 2022; 14(20):5046. https://doi.org/10.3390/cancers14205046
Chicago/Turabian StyleGrottoli, Melania, Paolo Carrega, Lodovica Zullo, Chiara Dellepiane, Giovanni Rossi, Francesca Parisi, Giulia Barletta, Linda Zinoli, Simona Coco, Angela Alama, and et al. 2022. "Immune Checkpoint Blockade: A Strategy to Unleash the Potential of Natural Killer Cells in the Anti-Cancer Therapy" Cancers 14, no. 20: 5046. https://doi.org/10.3390/cancers14205046