ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
The IL-15-Based ALT-803 Complex Enhances FcγRIIIa-Triggered NK Cell Responses and In Vivo Clearance of B Cell Lymphomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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101 citing papers in PubMed, 144 citations in OpenAlex.
- Fc-engineered anti-CD33 monoclonal antibody potentiates cytotoxicity of membrane-bound interleukin-21 expanded natural killer cells in acute myeloid leukemia.Cytotherapy · 2020Trial
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- Advances in IL-15-Based Cancer Immunotherapy and Divergent Immunological Effects of IL-2 and IL-15 Signaling via the Shared IL-2Rβγ Receptor.Frontiers in immunology · 2026Review
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Leveraging the heterogeneity of the NK cell repertoire for the development of immunotherapies for acute leukemia.Journal of translational medicine · 2025Review
- Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- Dual T/NK cell engagement via B7-H6-targeted bispecific antibodies and IL-15 eradicates chemo-resistant solid tumors.Frontiers in immunology · 2025Article
- Natural killer cell biology and therapy in multiple myeloma: challenges and opportunities.Experimental hematology & oncology · 2024Review
- Targeting sinonasal undifferentiated carcinoma with a combinatory immunotherapy approach.Translational oncology · 2024Article
- IL-15 Priming Alters IFN-γ Regulation in Murine NK Cells.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
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- Combined use of NK cells and radiotherapy in the treatment of solid tumors.Frontiers in immunology · 2023Review
- The role of interleukin-15 in the development and treatment of hematological malignancies.Frontiers in immunology · 2023Review
- Article
- Pre-Existing HSV-1 Immunity Enhances Anticancer Efficacy of a Novel Immune-Stimulating Oncolytic Virus.Viruses · 2022Article
- IL-15 Superagonist N-803 Enhances IFN-γ Production of MAIT Cells in SIVInfection and immunity · 2022Article
- Natural killer cells in antitumour adoptive cell immunotherapy.Nature reviews. Cancer · 2022Review
- Development and Characterization of an Anti-Cancer Monoclonal Antibody for Treatment of Human Carcinomas.Cancers · 2022Review
- HIV-1 Reservoir Persistence and Decay: Implications for Cure Strategies.Current HIV/AIDS reports · 2022Review
41 more citing papers are in PubMed but not listed here.
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21 authors at 1 institution in 1 country.
Funding
Abstract
purposeAnti-CD20 monoclonal antibodies (mAb) are an important immunotherapy for B-cell lymphoma, and provide evidence that the immune system may be harnessed as an effective lymphoma treatment approach. ALT-803 is a superagonist IL-15 mutant and IL-15Rα-Fc fusion complex that activates the IL-15 receptor constitutively expressed on natural killer (NK) cells. We hypothesized that ALT-803 would enhance anti-CD20 mAb-directed NK-cell responses and antibody-dependent cellular cytotoxicity (ADCC). EXPERIMENTAL
designWe tested this hypothesis by adding ALT-803 immunostimulation to anti-CD20 mAb triggering of NK cells in vitro and in vivo. Cell lines and primary human lymphoma cells were utilized as targets for primary human NK cells. Two complementary in vivo mouse models were used, which included human NK-cell xenografts in NOD/SCID-γc (-/-) mice.
resultsWe demonstrate that short-term ALT-803 stimulation significantly increased degranulation, IFNγ production, and ADCC by human NK cells against B-cell lymphoma cell lines or primary follicular lymphoma cells. ALT-803 augmented cytotoxicity and the expression of granzyme B and perforin, providing one potential mechanism for this enhanced functionality. Moreover, in two distinct in vivo B-cell lymphoma models, the addition of ALT-803 to anti-CD20 mAb therapy resulted in significantly reduced tumor cell burden and increased survival. Long-term ALT-803 stimulation of human NK cells induced proliferation and NK-cell subset changes with preserved ADCC.
conclusionsALT-803 represents a novel immunostimulatory drug that enhances NK-cell antilymphoma responses in vitro and in vivo, thereby supporting the clinical investigation of ALT-803 plus anti-CD20 mAbs in patients with indolent B-cell lymphoma.
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