ArticleClinical & translational immunology2019
Dual targeting of RANKL and PD-1 with a bispecific antibody improves anti-tumor immunity.
Article in Clinical & translational immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 21 papers.
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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.
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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
21 citing papers in PubMed, 27 citations in OpenAlex.
- Research trends and highlights in PD-1/PD-L1 inhibitor immunotherapy in lung cancer: a bibliometric analysis.Discover oncology · 2025Article
- Targets Selection for Precision Therapy of Relapsed/Refractory Multiple Myeloma: the Latest Advancements.Current treatment options in oncology · 2025Review
- Repurposing drugs for solid tumor treatment: focus on immune checkpoint inhibitors.Cancer biology & medicine · 2023Review
- Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: An exploratory analysis.Journal of bone oncology · 2022Article
- Extensive plasma proteomic profiling revealed receptor activator of nuclear factor kappa-Β ligand (RANKL) as emerging biomarker of nivolumab clinical benefit in patients with metastatic renal cell carcinoma.Journal for immunotherapy of cancer · 2022Article
- RANKL biology.Bone · 2022Review
- Enabling the next steps in cancer immunotherapy: from antibody-based bispecifics to multispecifics, with an evolving role for bioconjugation chemistry.RSC chemical biology · 2022Review
- Bispecific Antibodies Progression in Malignant Melanoma.Frontiers in pharmacology · 2022Review
- Roles of the RANKL-RANK Axis in Immunity-Implications for Pathogenesis and Treatment of Bone Metastasis.Frontiers in immunology · 2022Review
- The roles of PD-1/PD-L1 in the prognosis and immunotherapy of prostate cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Immuno-PET Molecular Imaging of RANKL in Cancer.Cancers · 2021Article
- Atezolizumab alleviates the immunosuppression induced by PD‑L1‑positive neutrophils and improves the survival of mice during sepsis.Molecular medicine reports · 2021Article
- Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy.Frontiers in immunology · 2021Review
- Role of RANKL in cancer development and metastasis.Journal of bone and mineral metabolism · 2021Review
- The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL.International journal of molecular sciences · 2020Review
- Exploration of the personalized immune checkpoint atlas of plasma cell dyscrasias patients using high‑dimensional single‑cell analysis.Oncology reports · 2020Article
- Combined Anti-Cancer Strategies Based on Anti-Checkpoint Inhibitor Antibodies.Antibodies (Basel, Switzerland) · 2020Review
- Review
- Targeting the RANKL/RANK/OPG Axis for Cancer Therapy.Frontiers in oncology · 2020Review
- Structure and Optimization of Checkpoint Inhibitors.Cancers · 2019Review
Corrections and comments
- Retraction · 2022-02-23Falsification/Fabrication of Image · Investigation by Company/Institution · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe addition of RANKL/RANK blockade to immune checkpoint inhibitors (ICIs) such as anti-PD-1/PD-L1 and anti-CTLA4 antibodies is associated with increased anti-tumor immunity in mice. Recent retrospective clinical studies in patients with advanced melanoma and lung cancer suggest the addition of anti-RANKL antibody to ICI increases the overall response rate relative to ICI treatment alone. Based on this rationale, we developed a novel bispecific antibody (BsAb) co-targeting RANKL and PD-1.
methodsWe characterized target binding and functional activity of the anti-RANKL/PD-1 BsAb in cell-based assays. Anti-tumor activity was confirmed in experimental lung metastasis models and in mice with established subcutaneously transplanted tumors.
resultsThe anti-RANKL/PD-1 BsAb retained binding to both RANKL and PD-1 and blocked the interaction with respective counter-structures RANK and PD-L1. The inhibitory effect of anti-RANKL/PD-1 BsAb was confirmed by demonstrating a complete block of RANKL-dependent osteoclast formation. Monotherapy activity of anti-RANKL/PD-1 BsAb was observed in anti-PD-1 resistant tumors and, when combined with anti-CTLA-4 mAb, increased anti-tumor responses. An equivalent or superior anti-tumor response was observed with the anti-RANKL/PD-1 BsAb compared with the combination of parental anti-RANKL plus anti-PD-1 antibodies depending upon the tumor model. DISCUSSION: Mechanistically, the anti-tumor activity of anti-RANKL/PD-1 BsAb required CD8
conclusionIn summary, the bispecific anti-RANKL/PD-1 antibody demonstrates potent tumor growth inhibition in settings of ICI resistance and represents a novel modality for clinical development in advanced cancer.
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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.