ArticleJournal for immunotherapy of cancer2014
Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study.
Article in Journal for immunotherapy of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00389285 (A Phase 1/2, Open-Label, Dose Escalation Study to Assess the Safety and Pharmacokinetics of Recombinant Interleukin 21), which is not on this map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1/2, Open-Label, Dose Escalation Study to Assess the Safety and Pharmacokinetics of Recombinant Interleukin 21 (rIL-21) Administered Concomitantly With Sorafenib (Nexavar) in Subjects With Metastatic Renal Cell Carcinoma
Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Design of a potent interleukin-21 mimic for cancer immunotherapy.Science immunology · 2025Article
- Interleukin-21 engineering enhances CD19-specific CAR-NK cell activity against B-cell lymphoma via enriched metabolic pathways.Experimental hematology & oncology · 2025Article
- The role of immunotherapy in targeting tumor microenvironment in genitourinary cancers.Frontiers in immunology · 2025Review
- Personalized Antifibrotic Therapy in CKD Progression.Journal of personalized medicine · 2024Review
- Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.Cancer cell · 2024Article
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- From bench to bedside: the past, present and future of IL-21 immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.Cancer immunology, immunotherapy : CII · 2024Article
- Therapeutic potential of interleukin-21 in cancer.Frontiers in immunology · 2024Review
- Cytokine conjugation to enhance T cell therapy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy.Journal for immunotherapy of cancer · 2022Article
- Roles for macrophage-polarizing interleukins in cancer immunity and immunotherapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Review
- The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?Biomedicines · 2022Review
- New developments implicating IL-21 in autoimmune disease.Journal of autoimmunity · 2021Review
- The Half-Life-Extended IL21 can Be Combined With Multiple Checkpoint Inhibitors for Tumor Immunotherapy.Frontiers in cell and developmental biology · 2021Article
- Adenovirus-mediated overexpression of interleukin-21 regulates the development of oral squamous cell carcinomaOncology letters · 2020Article
- Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors.Frontiers in oncology · 2019Review
- Cytokines in Cancer Immunotherapy.Cold Spring Harbor perspectives in biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor.
methodsIn this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10-50 mcg/kg) on days 1-5 and 15-19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated.
resultsIn phase 1 (n = 19), the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg/kg/day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib.
conclusionIL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC.
trial registrationClinicalTrials.gov Identifier: NCT00389285.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.