{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:14:52Z","timestamp":1789766092896,"version":"4.0.1"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health","award":["ZIA BC 010944"],"award-info":[{"award-number":["ZIA BC 010944"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Identifying effective immunotherapies for solid tumors remains challenging despite the significant clinical responses observed in subsets of patients treated with immune checkpoint inhibitors. Interleukin-15 (IL-15) is a promising cytokine for the treatment of cancer as it stimulates NK and CD8+ lymphocytes. However, unfavorable pharmacokinetics and safety concerns render recombinant IL-15 (rIL-15) a less attractive modality. These shortcomings were addressed by the clinical development of heterodimeric IL-15 agonists, including N803. In preclinical tumor models, N803 elicited significant Th1 immune activation and tumor suppressive effects, primarily mediated by NK and CD8+ T lymphocytes. In addition, multiple clinical studies have demonstrated N803 to be safe for the treatment of cancer patients. The combination of N803 with the immune checkpoint inhibitor nivolumab demonstrated encouraging clinical responses in nivolumab-na\u00efve and nivolumab-refractory patients with non-small cell lung cancer. In a recent Phase II\/III clinical study, most Bacillus Calmette\u2013Guerin (BCG)-refractory bladder cancer patients treated with N803 plus BCG experienced durable complete responses. Currently, N803 is being evaluated preclinically and clinically in combination with various agents, including chemotherapeutics, immune checkpoint inhibitors, vaccines, and other immuno-oncology agents. This report will review the mechanism(s) of action of N803 and how it relates to the preclinical and clinical studies of N803.<\/jats:p>","DOI":"10.3390\/cells12121611","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T01:35:30Z","timestamp":1686620130000},"page":"1611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies"],"prefix":"10.3390","volume":"12","author":[{"given":"Grace","family":"Lui","sequence":"first","affiliation":[{"name":"Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-9459","authenticated-orcid":false,"given":"Christine M.","family":"Minnar","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Soon-Shiong","sequence":"additional","affiliation":[{"name":"ImmunityBio, Culver City, CA 90232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7932-4072","authenticated-orcid":false,"given":"Jeffrey","family":"Schlom","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-8122","authenticated-orcid":false,"given":"Sofia R.","family":"Gameiro","sequence":"additional","affiliation":[{"name":"Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fimmu.2019.00263","article-title":"Fueling Cancer Immunotherapy with Common Gamma Chain Cytokines","volume":"10","author":"Dwyer","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101307","DOI":"10.1016\/j.smim.2019.101307","article-title":"Common gamma chain cytokines and CD8 T cells in cancer","volume":"42","author":"Shourian","year":"2019","journal-title":"Semin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1182\/blood-2011-10-384362","article-title":"Circulating IL-15 exists as heterodimeric complex with soluble IL-15Ralpha in human and mouse serum","volume":"120","author":"Bergamaschi","year":"2012","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1074-7613(02)00429-6","article-title":"IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells","volume":"17","author":"Dubois","year":"2002","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.imlet.2017.08.010","article-title":"The potential and promise of IL-15 in immuno-oncogenic therapies","volume":"190","author":"Robinson","year":"2017","journal-title":"Immunol. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3654","DOI":"10.1002\/j.1460-2075.1995.tb00035.x","article-title":"Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor","volume":"14","author":"Giri","year":"1995","journal-title":"EMBO J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.4049\/jimmunol.158.6.2610","article-title":"Induction of IL-15 messenger RNA and protein in human blood-derived dendritic cells: A role for IL-15 in attraction of T cells","volume":"158","author":"Jonuleit","year":"1997","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1172\/JCI118321","article-title":"Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro","volume":"96","author":"Carson","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"735","DOI":"10.4049\/jimmunol.156.2.735","article-title":"Induction and regulation of IL-15 expression in murine macrophages","volume":"156","author":"Doherty","year":"1996","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.4049\/jimmunol.1301389","article-title":"Transcriptional regulation of IL-15 expression during hematopoiesis","volume":"191","author":"Colpitts","year":"2013","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1073\/pnas.1318281111","article-title":"Characterization of the IL-15 niche in primary and secondary lymphoid organs in vivo","volume":"111","author":"Cui","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1158\/1078-0432.CCR-12-3603","article-title":"Molecular pathways: Interleukin-15 signaling in health and in cancer","volume":"20","author":"Mishra","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.tips.2011.09.004","article-title":"Interleukin-15 biology and its therapeutic implications in cancer","volume":"33","author":"Steel","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.immunol.17.1.19","article-title":"The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens","volume":"17","author":"Waldmann","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1084\/jem.191.5.771","article-title":"Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice","volume":"191","author":"Kennedy","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3810","DOI":"10.1073\/pnas.95.7.3810","article-title":"Cytokine-induced survival of activated T cells in vitro and in vivo","volume":"95","author":"Vella","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11445","DOI":"10.1073\/pnas.200363097","article-title":"IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice","volume":"97","author":"Dubois","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1158\/2326-6066.CIR-15-0009","article-title":"The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: Implications for cancer therapy","volume":"3","author":"Waldmann","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ni1263","article-title":"A function for interleukin 2 in Foxp3-expressing regulatory T cells","volume":"6","author":"Fontenot","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nri1901","article-title":"The biology of interleukin-2 and interleukin-15: Implications for cancer therapy and vaccine design","volume":"6","author":"Waldmann","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S1074-7613(00)80564-6","article-title":"Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15","volume":"8","author":"Zhang","year":"1998","journal-title":"Immunity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1182\/blood-2003-08-2814","article-title":"Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cells","volume":"103","author":"Schluns","year":"2004","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1182\/blood.V97.1.14","article-title":"Interleukin 15: Biology and relevance to human disease","volume":"97","author":"Fehniger","year":"2001","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"868","DOI":"10.3389\/fimmu.2020.00868","article-title":"IL-15 in the Combination Immunotherapy of Cancer","volume":"11","author":"Waldmann","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.it.2022.08.004","article-title":"Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy","volume":"43","author":"Ma","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1172\/JCI59535","article-title":"IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity","volume":"122","author":"Liu","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E10915","DOI":"10.1073\/pnas.1811615115","article-title":"IL-15 enhanced antibody-dependent cellular cytotoxicity mediated by NK cells and macrophages","volume":"115","author":"Zhang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"228ra37","DOI":"10.1126\/scitranslmed.3007240","article-title":"Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients","volume":"6","author":"Mlecnik","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1200\/JCO.2014.57.3329","article-title":"Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer","volume":"33","author":"Conlon","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1158\/2326-6066.CIR-17-0279","article-title":"IL15 Infusion of Cancer Patients Expands the Subpopulation of Cytotoxic CD56(bright) NK Cells and Increases NK-Cell Cytokine Release Capabilities","volume":"5","author":"Dubois","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1158\/1078-0432.CCR-17-2451","article-title":"A First-in-Human Phase I Study of Subcutaneous Outpatient Recombinant Human IL15 (rhIL15) in Adults with Advanced Solid Tumors","volume":"24","author":"Miller","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e20191062","DOI":"10.1084\/jem.20191062","article-title":"Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer","volume":"217","author":"Waldmann","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Bergamaschi, C., Stravokefalou, V., Stellas, D., Karaliota, S., Felber, B.K., and Pavlakis, G.N. (2021). Heterodimeric IL-15 in Cancer Immunotherapy. Cancers, 13.","DOI":"10.3390\/cancers13040837"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1080\/14712598.2020.1738379","article-title":"Rationale for IL-15 superagonists in cancer immunotherapy","volume":"20","author":"Knudson","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1074\/jbc.M705725200","article-title":"Intracellular interaction of interleukin-15 with its receptor alpha during production leads to mutual stabilization and increased bioactivity","volume":"283","author":"Bergamaschi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.cyto.2011.09.028","article-title":"IL-15:IL-15 receptor alpha superagonist complex: High-level co-expression in recombinant mammalian cells, purification and characterization","volume":"56","author":"Han","year":"2011","journal-title":"Cytokine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.4049\/jimmunol.0901244","article-title":"Novel human interleukin-15 agonists","volume":"183","author":"Zhu","year":"2009","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10719-015-9627-1","article-title":"Recombinant human heterodimeric IL-15 complex displays extensive and reproducible N- and O-linked glycosylation","volume":"33","author":"Chertova","year":"2016","journal-title":"Glycoconj. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16130","DOI":"10.18632\/oncotarget.7470","article-title":"IL-15 superagonist\/IL-15RalphaSushi-Fc fusion complex (IL-15SA\/IL-15RalphaSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity against murine breast and colon carcinomas","volume":"7","author":"Kim","year":"2016","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cyto.2017.12.003","article-title":"Evaluation of the biological activities of the IL-15 superagonist complex, ALT-803, following intravenous versus subcutaneous administration in murine models","volume":"107","author":"Liu","year":"2018","journal-title":"Cytokine"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1158\/2326-6066.CIR-15-0093-T","article-title":"Comparison of the Superagonist Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models","volume":"4","author":"Rhode","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/ijc.29686","article-title":"Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model","volume":"138","author":"Mathios","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1040669","DOI":"10.3389\/fimmu.2022.1040669","article-title":"ALT-803 in the treatment of non-muscle-invasive bladder cancer: Preclinical and clinical evidence and translational potential","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e005752","DOI":"10.1136\/jitc-2022-005752","article-title":"Exploiting the immunogenic potential of standard of care radiation or cisplatin therapy in preclinical models of HPV-associated malignancies","volume":"10","author":"Kowalczyk","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e002258","DOI":"10.1136\/jitc-2020-002258","article-title":"Exploiting off-target effects of estrogen deprivation to sensitize estrogen receptor negative breast cancer to immune killing","volume":"9","author":"Wolfson","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s00262-018-2121-4","article-title":"An IL-15 superagonist\/IL-15Ralpha fusion complex protects and rescues NK cell-cytotoxic function from TGF-beta1-mediated immunosuppression","volume":"67","author":"Fujii","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1172\/JCI90387","article-title":"CD56bright NK cells exhibit potent antitumor responses following IL-15 priming","volume":"127","author":"Wagner","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1007\/s00262-020-02749-8","article-title":"IL-15 superagonist N-803 improves IFNgamma production and killing of leukemia and ovarian cancer cells by CD34(+) progenitor-derived NK cells","volume":"70","author":"Maas","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e002267","DOI":"10.1136\/jitc-2020-002267","article-title":"Combinatorial immunotherapy of N-803 (IL-15 superagonist) and dinutuximab with ex vivo expanded natural killer cells significantly enhances in vitro cytotoxicity against GD2(+) pediatric solid tumors and in vivo survival of xenografted immunodeficient NSG mice","volume":"9","author":"Chu","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jtho.2022.11.008","article-title":"An Interleukin-15 Superagonist Enables Antitumor Efficacy of Natural Killer Cells Against All Molecular Variants of SCLC","volume":"18","author":"Fousek","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s40425-019-0551-y","article-title":"Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy","volume":"7","author":"Knudson","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e001691","DOI":"10.1136\/jitc-2020-001691","article-title":"Differential combination immunotherapy requirements for inflamed (warm) tumors versus T cell excluded (cool) tumors: Engage, expand, enable, and evolve","volume":"9","author":"Fabian","year":"2021","journal-title":"J. ImmunoTherapy Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1158\/2326-6066.CIR-22-0600","article-title":"Reverse translation identifies the synergistic role of immune checkpoint blockade and IL-15 to enhance immunotherapy of ovarian cancer","volume":"11","author":"Felices","year":"2023","journal-title":"Cancer Immunol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1158\/2767-9764.CRC-21-0020","article-title":"Combinatorial Natural Killer Cell-based Immunotherapy Approaches Selectively Target Chordoma Cancer Stem Cells","volume":"1","author":"Hoke","year":"2021","journal-title":"Cancer Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e000450","DOI":"10.1136\/jitc-2019-000450","article-title":"PD-L1 targeting high-affinity NK (t-haNK) cells induce direct antitumor effects and target suppressive MDSC populations","volume":"8","author":"Fabian","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1158\/1078-0432.CCR-19-0727","article-title":"Cooperative Immune-Mediated Mechanisms of the HDAC Inhibitor Entinostat, an IL15 Superagonist, and a Cancer Vaccine Effectively Synergize as a Novel Cancer Therapy","volume":"26","author":"Hicks","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1158\/2326-6066.CIR-20-0638","article-title":"Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune-Tumor Interactions: Engage, Expand, Enable","volume":"9","author":"Fabian","year":"2021","journal-title":"Cancer Immunol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gomes-Giacoia, E., Miyake, M., Goodison, S., Sriharan, A., Zhang, G., You, L., Egan, J.O., Rhode, P.R., Parker, A.S., and Chai, K.X. (2014). Intravesical ALT-803 and BCG treatment reduces tumor burden in a carcinogen induced bladder cancer rat model; a role for cytokine production and NK cell expansion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096705"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.4049\/jimmunol.2100066","article-title":"Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric IL-15 Superagonist, in Healthy Volunteers","volume":"208","author":"Rubinstein","year":"2022","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5552","DOI":"10.1158\/1078-0432.CCR-18-0945","article-title":"Phase I trial of ALT-803, a novel recombinant IL15 complex, in patients with advanced solid tumors","volume":"24","author":"Margolin","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1182\/blood-2017-12-823757","article-title":"First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation","volume":"131","author":"Romee","year":"2018","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S1470-2045(18)30148-7","article-title":"ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: A non-randomised, open-label, phase 1b trial","volume":"19","author":"Wrangle","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e001098","DOI":"10.1136\/jitc-2020-001098","article-title":"Complete response to avelumab and IL-15 superagonist N-803 with Abraxane in Merkel cell carcinoma: A case study","volume":"8","author":"Drusbosky","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/JU.0000000000002957","article-title":"Clinical and Preclinical Therapies for Bladder Cancer Following Bacillus Calmette-Guerin Failure","volume":"209","author":"Nazmifar","year":"2023","journal-title":"J. Urol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1080\/14712598.2022.2082869","article-title":"Emerging treatment landscape of non-muscle invasive bladder cancer","volume":"22","author":"Valenza","year":"2022","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"abstr 510","DOI":"10.1200\/JCO.2018.36.6_suppl.510","article-title":"Phase Ib trial of ALT-803, an IL-15 superagonist, plus BCG for the treatment of BCG-na\u00efve patients with non-muscle-invasive bladder cancer. ASCO 2018 Genitourinary Cancers Symposium Proceedings","volume":"36","author":"Rosser","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1912885","DOI":"10.1080\/2162402X.2021.1912885","article-title":"Safety, Tolerability, and Long-Term Clinical Outcomes of an IL-15 analogue (N-803) Admixed with Bacillus Calmette-Guerin (BCG) for the Treatment of Bladder Cancer","volume":"10","author":"Rosser","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"abstr 4508","DOI":"10.1200\/JCO.2022.40.16_suppl.4508","article-title":"Final clinical results of pivotal trial of IL-15R\u03b1Fc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC)","volume":"40","author":"Chamie","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1158\/2326-6066.CIR-15-0176","article-title":"Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor","volume":"4","author":"Vandeveer","year":"2016","journal-title":"Cancer Immunol. 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