ArticlePloS one2014
Direct T cell activation via CD40 ligand generates high avidity CD8+ T cells capable of breaking immunological tolerance for the control of tumors.
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 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
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- Advanced Acral Melanoma Therapies: Current Status and Future Directions.Current treatment options in oncology · 2022Review
- Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer.Biomedicines · 2021Review
- Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance.Cancer metastasis reviews · 2021Review
- Plasma-Activated Medium Potentiates the Immunogenicity of Tumor Cell Lysates for Dendritic Cell-Based Cancer Vaccines.Cancers · 2021Article
- Monocytes, Macrophages, and Their Potential Niches in Synovial Joints - Therapeutic Targets in Post-Traumatic Osteoarthritis?Frontiers in immunology · 2021Review
- Anti-CD40 Antibody Fused to CD40 Ligand Is a Superagonist Platform for Adjuvant Intrinsic DC-Targeting Vaccines.Frontiers in immunology · 2021Article
- Immune-phenotyping of pleomorphic dermal sarcomas suggests this entity as a potential candidate for immunotherapy.Cancer immunology, immunotherapy : CII · 2019Article
- Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance.Cell reports · 2018Article
- CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal.Central-European journal of immunology · 2018Article
- A pilot study of the immunogenicity of a 9-peptide breast cancer vaccine plus poly-ICLC in early stage breast cancer.Journal for immunotherapy of cancer · 2017Article
- Trial watch: Naked and vectored DNA-based anticancer vaccines.Oncoimmunology · 2015Article
- DNA vaccine elicits an efficient antitumor response by targeting the mutant Kras in a transgenic mouse lung cancer model.Gene therapy · 2014Article
- DNA vaccine for cancer immunotherapy.Human vaccines & immunotherapeutics · 2014Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 4 countries.
Funding
Abstract
CD40 and CD40 ligand (CD40L) are costimulatory molecules that play a pivotal role in the proinflammatory immune response. Primarily expressed by activated CD4+ T cells, CD40L binds to CD40 on antigen presenting cells (APCs), thereby inducing APC activation. APCs, in turn, prime cytotoxic T lymphocytes (CTLs). Here, two tumor-associated antigen (TAA) animal models, p53-based and GP100-based, were utilized to examine the ability of CD40-CD40L to improve antigen-specific CTL-mediated antitumor immune responses. Although p53 and GP100 are self-antigens that generate low affinity antigen-specific CD8+ T cells, studies have shown that their functional avidity can be improved with CD40L-expressing APCs. Therefore, in the current study, we immunized mice with a DNA construct encoding a TAA in conjunction with another construct encoding CD40L via intramuscular injection followed by electroporation. We observed a significant increase in the antigen-specific CTL-mediated immune responses as well as the potent antitumor effects in both models. Antibody depletion experiments demonstrated that CD8+ T cells play a crucial role in eliciting antitumor effects in vaccinated mice. Furthermore, we showed that in vitro stimulation with irradiated tumor cells expressing both TAA and CD40L improved the functional avidity of antigen-specific CD8+ T cells. Thus, our data show that vaccination with TAA/CD40L DNA can induce potent antitumor effects against TAA-expressing tumors through the generation of better functioning antigen-specific CD8+ T cells. Our study serves as an important foundation for future clinical translation.
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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.