Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies
Abstract
:1. Introduction
2. Recombinant IL-15 Studies
3. IL-15 Heterodimeric Agonists
4. N803
4.1. N803 as Single Agent
4.2. N803 in Combination Therapy
5. Clinical Studies Involving N803
5.1. Phase I Clinical Studies
5.2. N803 in Combination with Immune Checkpoint Inhibitors and Other Immuno-Oncology Agents
5.3. Clinical Application of N803 in Bladder Cancer
6. Discussion
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Indication | Combination Therapy | Stage | Phase | Trial Identifier |
---|---|---|---|---|
Bladder cancer | BCG | BCG-unresponsive non-muscle invasive | Phase II/III | NCT03022825 |
BCG | Non-muscle invasive | Phase I/II | NCT02138734 | |
Breast cancer | Multiple SOC and immunotherapies | TNBC after SOC | Phase I/II | NCT03387085 |
Sacituzumab, PD-L1 t-haNK, and SOC | TNBC after prior therapies | Phase I/II | NCT04927884 | |
Colorectal cancer | Multiple SOC and immunotherapies | Metastatic | Phase I/II | NCT03563157 |
Colorectal and small bowel cancers | CV301, M7824, and NHS-IL12 | Phase II | NCT04491955 | |
Gastroesophageal junction cancers and advanced HNSCC | Pembrolizumab and PD-L1 t-haNK | Recurrent or metastatic | Phase II | NCT04847466 |
Head and neck cancer | M7824 and TriAd vaccine (CEA/MUC1/Brachyury) | Resectable and not HPV associated | Phase I/II | NCT04247282 |
HNSCC | CIML NK cell infusion, and Ipilimumab | Recurrent | Phase I | NCT04290546 |
Non-small cell lung cancer | Nivolumab | Advanced or metastatic | Phase I/II | NCT02523469 |
Pembrolizumab and multiple SOC | Stage 3 or 4 | Phase III | NCT03520686 | |
Pembrolizumab and multiple SOC | Advanced, recurrent, or Stages 3–4B | Phase II/III | NCT05096663 | |
Lung (NSCLC/SCLC), urothelial, HNSCC, MCC, melanoma, RCC, gastric, cervical, hepatocellular, MSI, dMMR, and colorectal | Pembrolizumab, Nivolumab, Atezolizumab, Avelumab, Durvalumab, and PD-L1 t-haNK | Prior immune checkpoint inhibitors | Phase II | NCT03228667 |
Solid tumors | M-CENK | Advanced or metastatic | Phase I | NCT04898543 |
Pancreatic cancer | PD-L1 t-haNK, SBRT, and additional SOC | Locally advanced or metastatic | Phase II | NCT04390399 |
Prostate cancer and solid tumors | M7824, MVA/FP-Brachyury, and Epacadostat | Advanced or metastatic | Phase I/II | NCT03493945 |
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Lui, G.; Minnar, C.M.; Soon-Shiong, P.; Schlom, J.; Gameiro, S.R. Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies. Cells 2023, 12, 1611. https://doi.org/10.3390/cells12121611
Lui G, Minnar CM, Soon-Shiong P, Schlom J, Gameiro SR. Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies. Cells. 2023; 12(12):1611. https://doi.org/10.3390/cells12121611
Chicago/Turabian StyleLui, Grace, Christine M. Minnar, Patrick Soon-Shiong, Jeffrey Schlom, and Sofia R. Gameiro. 2023. "Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies" Cells 12, no. 12: 1611. https://doi.org/10.3390/cells12121611