ArticlePloS one2009
Nanoparticle-delivered multimeric soluble CD40L DNA combined with Toll-Like Receptor agonists as a treatment for melanoma.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 69 citations in OpenAlex.
- Computational analysis of CD40L missense variants A123E, S222F, and G257R predicts altered CD40 binding and trimeric stability in X-linked hyper-IgM syndrome.Frontiers in immunology · 2026Article
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Pushing the envelope: Immune mechanism and application landscape of macrophage-activating lipopeptide-2.Frontiers in immunology · 2023Review
- Controlled Modular Multivalent Presentation of the CD40 Ligand on P22 Virus-like Particles Leads to Tunable Amplification of CD40 Signaling.ACS applied bio materials · 2021Article
- Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Review
- Diamonds in the Rough: Harnessing Tumor-Associated Myeloid Cells for Cancer Therapy.Frontiers in immunology · 2018Review
- The era of bioengineering: how will this affect the next generation of cancer immunotherapy?Journal of translational medicine · 2017Review
- Effective Combination of Innate and Adaptive Immunotherapeutic Approaches in a Mouse Melanoma Model.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Anti-tumor Activity of Toll-Like Receptor 7 Agonists.Frontiers in pharmacology · 2017Review
- Biodegradable poly (lactic acid-co-glycolic acid) scaffolds as carriers for genetically-modified fibroblasts.PloS one · 2017Article
- In situ vaccination: Cancer immunotherapy both personalized and off-the-shelf.Molecular oncology · 2015Review
- Symmetry Controlled, Genetic Presentation of Bioactive Proteins on the P22 Virus-like Particle Using an External Decoration Protein.ACS nano · 2015Article
- Article
- Intratumoral immunotherapy for melanoma.Cancer immunology, immunotherapy : CII · 2015Review
- Review
- Dendritic Cell-Based Immunotherapy Treatment for Glioblastoma Multiforme.BioMed research international · 2015Review
- Nanocarrier-based immunotherapy in cancer management and research.ImmunoTargets and therapy · 2014Review
- Design of vaccine adjuvants incorporating TNF superfamily ligands and TNF superfamily molecular mimics.Immunologic research · 2013Review
- Delivery of host cell-directed therapeutics for intracellular pathogen clearance.Expert review of anti-infective therapy · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Stimulation of CD40 or Toll-Like Receptors (TLR) has potential for tumor immunotherapy. Combinations of CD40 and TLR stimulation can be synergistic, resulting in even stronger dendritic cell (DC) and CD8+ T cell responses. To evaluate such combinations, established B16F10 melanoma tumors were injected every other day X 5 with plasmid DNA encoding a multimeric, soluble form of CD40L (pSP-D-CD40L) either alone or combined with an agonist for TLR1/2 (Pam(3)CSK(4) ), TLR2/6 (FSL-1 and MALP2), TLR3 (polyinosinic-polycytidylic acid, poly(I:C)), TLR4 ( monophosphoryl lipid A, MPL), TLR7 (imiquimod), or TLR9 (Class B CpG phosphorothioate oligodeoxynucleotide, CpG). When used by itself, pSP-D-CD40L slowed tumor growth and prolonged survival, but did not lead to cure. Of the TLR agonists, CpG and poly(I:C) also slowed tumor growth, and the combination of these two TLR agonists was more effective than either agent alone. The triple combination of intratumoral pSP-D-CD40L + CpG + poly(I:C) markedly slowed tumor growth and prolonged survival. This treatment was associated with a reduction in intratumoral CD11c+ dendritic cells and an influx of CD8+ T cells. Since intratumoral injection of plasmid DNA does not lead to efficient transgene expression, pSP-D-CD40L was also tested with cationic polymers that form DNA-containing nanoparticles which lead to enhanced intratumoral gene expression. Intratumoral injections of pSP-D-CD40L-containing nanoparticles formed from polyethylenimine (PEI) or C32 (a novel biodegradable poly(B-amino esters) polymer) in combination with CpG + poly(I:C) had dramatic antitumor effects and frequently cured mice of B16F10 tumors. These data confirm and extend previous reports that CD40 and TLR agonists are synergistic and demonstrate that this combination of immunostimulants can significantly suppress tumor growth in mice. In addition, the enhanced effectiveness of nanoparticle formulations of DNA encoding immunostimulatory molecules such as multimeric, soluble CD40L supports the further study of this technology for tumor immunotherapy.
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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.