ArticleCancer immunology research2014
Targeting 4-1BB costimulation to the tumor stroma with bispecific aptamer conjugates enhances the therapeutic index of tumor immunotherapy.
Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed.
- Molecular Engineering of Aptamers for Glioblastoma Therapy: From Simple Antagonists to AI-Driven Approaches, a Narrative Review.International journal of molecular sciences · 2026Review
- The emerging role of aptamers in targeted cancer immunotherapy.Molecular therapy. Oncology · 2026Review
- Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Aptamers as target-specific recognition elements in drug delivery.Advanced drug delivery reviews · 2025Review
- Bispecific immunotherapy based on antibodies, T-cell receptors, and aptamers: mechanisms of action, adverse effects, and future perspectives.Frontiers in immunology · 2025Review
- Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy.Cell biochemistry and biophysics · 2024Review
- Aptamers as an approach to targeted cancer therapy.Cancer cell international · 2024Review
- Therapeutic immunomodulation by rationally designed nucleic acids and nucleic acid nanoparticles.Frontiers in immunology · 2023Review
- Cancer immunomodulation using bispecific aptamers.Molecular therapy. Nucleic acids · 2022Review
- RNA-mediated immunotherapy regulating tumor immune microenvironment: next wave of cancer therapeutics.Molecular cancer · 2022Review
- Evaluation of cancer immunotherapy using mini-tumor chips.Theranostics · 2022Article
- Aptamers: Cutting edge of cancer therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- The Potential of Aptamer-Mediated Liquid Biopsy for Early Detection of Cancer.International journal of molecular sciences · 2021Review
- Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors.Frontiers in cell and developmental biology · 2021Review
- Immune Modulatory Short Noncoding RNAs Targeting the Glioblastoma Microenvironment.Frontiers in oncology · 2021Review
- The Limitless Future of RNA Therapeutics.Frontiers in bioengineering and biotechnology · 2021Review
- Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule.Cell reports. Medicine · 2020Article
- Review
- Aptamer-Based In Vivo Therapeutic Targeting of Glioblastoma.Molecules (Basel, Switzerland) · 2020Review
- Aptamers, the Nucleic Acid Antibodies, in Cancer Therapy.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Despite the recent successes of using immune modulatory Abs in patients with cancer, autoimmune pathologies resulting from the activation of self-reactive T cells preclude the dose escalations necessary to fully exploit their therapeutic potential. To reduce the observed and expected toxicities associated with immune modulation, here we describe a clinically feasible and broadly applicable approach to limit immune costimulation to the disseminated tumor lesions of the patient, whereby an agonistic 4-1BB oligonucleotide aptamer is targeted to the tumor stroma by conjugation to an aptamer that binds to a broadly expressed stromal product, VEGF. This approach was predicated on the premise that by targeting the costimulatory ligands to products secreted into the tumor stroma, the T cells will be costimulated before their engagement of the MHC-peptide complex on the tumor cell, thereby obviating the need to target the costimulatory ligands to noninternalizing cell surface products expressed on the tumor cells. Underscoring the potency of stroma-targeted costimulation and the broad spectrum of tumors secreting VEGF, in preclinical murine tumor models, systemic administration of the VEGF-targeted 4-1BB aptamer conjugates engendered potent antitumor immunity against multiple unrelated tumors in subcutaneous, postsurgical lung metastasis, methylcholantrene-induced fibrosarcoma, and oncogene-induced autochthonous glioma models, and exhibited a superior therapeutic index compared with nontargeted administration of an agonistic 4-1BB Ab or 4-1BB aptamer.
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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.