ArticleThe Journal of clinical investigation2011
A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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
41 citing papers in PubMed, 54 citations in OpenAlex.
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- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- MyD88-mediated chimaeric antigen receptor macrophages suppress brain metastasis using target-specific phagocytosis.Nature biomedical engineering · 2026Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.Nature communications · 2024Article
- Azoximer bromide and hydroxyapatite: promising immune adjuvants in cancer.Cancer biology & medicine · 2024Review
- Getting (T cells) ENGaged.Haematologica · 2023Article
- Improving the anti-acute myeloid leukemia activity of CD123-specific engager T cells by MyD88 and CD40 costimulation.Haematologica · 2023Article
- Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages.Frontiers in immunology · 2023Article
- Navigating CAR-T cells through the solid-tumour microenvironment.Nature reviews. Drug discovery · 2021Review
- Review
- Engineering Supramolecular Organizing Centers for Optogenetic Control of Innate Immune Responses.Advanced biology · 2021Article
- Engineering Tolerance toward Allogeneic CAR-T Cells by Regulation of MHC Surface Expression with Human Herpes Virus-8 Proteins.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Engineering precision therapies: lessons and motivations from the clinic.Synthetic biology (Oxford, England) · 2021Review
- Metabolic engineering generates a transgene-free safety switch for cell therapy.Nature biotechnology · 2020Article
- Therapeutic vaccines for aggressive B-cell lymphoma.Leukemia & lymphoma · 2020Article
- Inducible MyD88/CD40 synergizes with IL-15 to enhance antitumor efficacy of CAR-NK cells.Blood advances · 2020Article
- Externally-Controlled Systems for Immunotherapy: From Bench to Bedside.Frontiers in immunology · 2020Review
- Article
- Two-Dimensional Regulation of CAR-T Cell Therapy with Orthogonal Switches.Molecular therapy oncolytics · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The in vivo therapeutic efficacy of DC-based cancer vaccines is limited by suboptimal DC maturation protocols. Although delivery of TLR adjuvants systemically boosts DC-based cancer vaccine efficacy, it could also increase toxicity. Here, we have engineered a drug-inducible, composite activation receptor for DCs (referred to herein as DC-CAR) comprising the TLR adaptor MyD88, the CD40 cytoplasmic region, and 2 ligand-binding FKBP12 domains. Administration of a lipid-permeant dimerizing ligand (AP1903) induced oligomerization and activation of this fusion protein, which we termed iMyD88/CD40. AP1903 administration to vaccinated mice enabled prolonged and targeted activation of iMyD88/CD40-modified DCs. Compared with conventionally matured DCs, AP1903-activated iMyD88/CD40-DCs had increased activation of proinflammatory MAPKs. AP1903-activated iMyD88/CD40-transduced human or mouse DCs also produced higher levels of Th1 cytokines, showed improved migration in vivo, and enhanced both antigen-specific CD8+ T cell responses and innate NK cell responses. Furthermore, treatment with AP1903 in vaccinated mice led to robust antitumor immunity against preestablished E.G7-OVA lymphomas and aggressive B16.F10 tumors. Thus, the iMyD88/CD40 unified "switch" effectively and safely replaced exogenous adjuvant cocktails, allowing remote and sustained DC activation in vivo. DC "licensing" through iMyD88/CD40 may represent a mechanism by which to exploit the natural synergy between the TLR and CD40 signaling pathways in DCs using a single small molecule drug and could augment the efficacy of antitumor DC-based vaccines.
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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.