ArticlePloS one2014
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.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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.
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Who cites it
61 citing papers in PubMed, 88 citations in OpenAlex.
- Prolonged Progression-Free Survival, Disease-Free Survival, and Cystectomy Avoidance With IL-15 Receptor Lymphocyte-Stimulating Agent NAI Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin-Unresponsive Papillary-Only Nonmuscle-Invasive Bladder Cancer.The Journal of urology · 2026Trial
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- Durable Responses and Cystectomy Avoidance With Interleukin-15 Receptor Agonist NAI Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer With Carcinoma In Situ ± Papillary Disease.The Journal of urology · 2026Article
- Narrative Review of Potential Non-Surgical Treatments for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer.Journal of clinical medicine · 2026Review
- 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
- FDA Approval Summary: Nogapendekin Alfa Inbakicept-pmln with BCG for BCG-Unresponsive Carcinoma In Situ.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Nogapendekin alfa Inbakicept-pmln (Anktiva) with BCG: A Promising Arsenal in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer Intervention.Advanced pharmaceutical bulletin · 2025Article
- IL-15: from discovery to FDA approval.Journal of hematology & oncology · 2025Article
- Development of Novel Intravesical Formulation for Bladder Retention Targeting Bladder Disorders.Current drug targets · 2025Review
- Isotretinoin promotes elimination of translation-competent HIV latent reservoirs in CD4T cells.PLoS pathogens · 2024Article
- Nogapendekin alfa Inbakicept: First Approval.Drugs · 2024Review
- Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings.International urology and nephrology · 2024Article
- Therapeutic approaches to enhance natural killer cell cytotoxicity.Frontiers in immunology · 2024Review
- Review
- IL-15 and N-803 for HIV Cure Approaches.Viruses · 2023Review
- Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies.Cells · 2023Review
- Novel Delivery Mechanisms for Existing Systemic Agents and Emerging Therapies in Bladder Cancer.Bladder cancer (Amsterdam, Netherlands) · 2023Review
- NK Cell-Targeted Immunotherapies in Bladder Cancer: Beyond Checkpoint Inhibitors.Bladder cancer (Amsterdam, Netherlands) · 2023Review
- Pre-Existing HSV-1 Immunity Enhances Anticancer Efficacy of a Novel Immune-Stimulating Oncolytic Virus.Viruses · 2022Article
- The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?Biomedicines · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Intravesical Bacillus Calmette-Guérin (BCG) has been shown to induce a specific immunologic response (i.e., activation of IL-2 and effector T-cells), while preclinical studies using ALT-803 (mutated IL-15 analogue combined with IL-15Rα-Fc fusion) have shown promising results by prolonging the agent's half-life and stimulating CD8+ T-cells. Based on these results, we hypothesized that the intravesical administration of ALT-803 along with BCG will generate an immunologic response leading to significant bladder tumor burden reduction. Using a well-established carcinogen induced rat non-muscle invasive bladder cancer (NMIBC) model, we studied the effects of intravesical ALT-803 with and without BCG. Rat tissues were evaluated to document treatment response. Intravesical ALT-803 was safe and well tolerated alone and in combination with BCG. As a single treatment agent, ALT-803 reduced tumor burden by 35% compared to control whereas BCG alone only reduced tumor burden by 15%. However, the combination of ALT-803 plus BCG reduced tumor burden by 46% compared to control. Immune monitoring suggested that the antitumor response was linked to the production and secretion of IL-1α, IL-1β and RANTES, which in turn, induced the proliferation and activation of NK cells. Lastly, tumoral responses of the combinational treatment were associated with 76% reduction in angiogenesis, which is significantly higher than when assessed with either agent alone. The enhanced therapeutic index seen with this duplet provides justification for the development of this regimen for future clinical trials.
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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.