ArticleVaccine2015
A multi-trimeric fusion of CD40L and gp100 tumor antigen activates dendritic cells and enhances survival in a B16-F10 melanoma DNA vaccine model.
Article in Vaccine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 21 citations in OpenAlex.
- Genetically engineered IgG1 and nanobody oligomers acquire strong intrinsic CD40 agonism.Bioengineered · 2024Article
- Duck CD40L as an adjuvant enhances systemic immune responses of avian flavivirus DNA vaccine.NPJ vaccines · 2024Article
- Lentiviral Vectors as a Vaccine Platform against Infectious Diseases.Pharmaceutics · 2023Review
- FcγRs and Their Relevance for the Activity of Anti-CD40 Antibodies.International journal of molecular sciences · 2022Review
- Nanocarriers based on bacterial membrane materials for cancer vaccine delivery.Nature protocols · 2022Review
- A lentiviral vector expressing a dendritic cell-targeting multimer induces mucosal anti-mycobacterial CD4Mucosal immunology · 2022Article
- CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies.Cellular & molecular immunology · 2022Review
- Cancer DNA vaccines: current preclinical and clinical developments and future perspectives.Journal of experimental & clinical cancer research : CR · 2019Review
- The promise and challenges of immune agonist antibody development in cancer.Nature reviews. Drug discovery · 2018Review
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Vaccination with tumor-associated antigens can induce cancer-specific CD8+ T cells. A recent improvement has been the targeting of antigen to dendritic cells (DC) using antibodies that bind DC surface molecules. This study explored the use of multi-trimers of CD40L to target the gp100 melanoma tumor antigen to DC. The spontaneously-multimerizing gene Surfactant Protein D (SPD) was used to fuse gp100 tumor antigen and CD40L, creating the recombinant protein SPD-gp100-CD40L. This "third generation" DC-targeting vaccine was designed to both target antigen to DC and optimally activate dendritic cells by aggregating CD40 trimers on the DC membrane surface. SPD-gp100-CD40L expressed as a 110kDa protein. Analytical light scattering analysis gave elution data corresponding to 4-trimer and multi-trimer SPD-gp100-CD40L oligomers. The protein was biologically active on dendritic cells and induced CD40-mediated NF-κB signaling. DNA vaccination with SPD-gp100-CD40L plasmid, together with plasmids encoding IL-12p70 and GM-CSF, significantly enhanced survival and inhibited tumor growth in a B16-F10 melanoma model. Expression of gp100 and SPD-CD40L as separate molecules did not enhance survival, highlighting the requirement to encode gp100 within SPD-CD40L for optimal vaccine activity. These data support a model where DNA vaccination with SPD-gp100-CD40L targets gp100 to DC in situ, induces activation of these DC, and generates a protective anti-tumor response when given in combination with IL-12p70 and GM-CSF plasmids.
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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.