ArticleThe Journal of clinical investigation2018
Cancer vaccine formulation dictates synergy with CTLA-4 and PD-L1 checkpoint blockade therapy.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 80 citations in OpenAlex.
- Combining a Universal Telomerase Based Cancer Vaccine With Ipilimumab in Patients With Metastatic Melanoma - Five-Year Follow Up of a Phase I/IIa Trial.Frontiers in immunology · 2021Trial
- Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy.Nature communications · 2020Trial
- Combined Vaccination with NY-ESO-1 Protein, Poly-ICLC, and Montanide Improves Humoral and Cellular Immune Responses in Patients with High-Risk Melanoma.Cancer immunology research · 2020Trial
- A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund's adjuvant in melanoma patients.Journal for immunotherapy of cancer · 2019Trial
- Intramuscular plasmid DNA electroporation sequesters neoantigen-specific CD8Molecular therapy. Oncology · 2026Article
- Shaping Antitumor Immunity with Peptide Vaccines: Implications of Immune Modulation at the Vaccine Site.Vaccines · 2025Review
- DNA Methyltransferase Inhibition Upregulates the Costimulatory Molecule ICAM-1 and the Immunogenic Phenotype of Melanoma Cells.JID innovations : skin science from molecules to population health · 2025Article
- Cancer Vaccines and Beyond: The Transformative Role of Nanotechnology in Immunotherapy.Pharmaceutics · 2025Review
- Immunophenotyping of colon cancer for identification of potential antigens for colon cancer vaccines.Frontiers in oncology · 2025Article
- Identification of ferroptosis-associated tumor antigens as the potential targets to prevent head and neck squamous cell carcinoma.Genes & diseases · 2024Article
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- Discovery of lung adenocarcinoma tumor antigens and ferroptosis subtypes for developing mRNA vaccines.Scientific reports · 2024Article
- Review
- Activated B-Cells enhance epitope spreading to support successful cancer immunotherapy.Frontiers in immunology · 2024Review
- Tumor antigen-loaded AAV vaccine drives protective immunity in a melanoma animal model.Molecular therapy. Methods & clinical development · 2023Article
- Research progress of nanovaccine in anti-tumor immunotherapy.Frontiers in oncology · 2023Review
- Efficient Anti-Tumor Immunotherapy Using Tumor Epitope-Coated Biodegradable Nanoparticles Combined With Polyinosinic-Polycytidylic Acid and an Anti-PD1 Monoclonal Antibody.Immune network · 2022Article
- Peptide emulsions in incomplete Freund's adjuvant create effective nurseries promoting egress of systemic CD4Journal for immunotherapy of cancer · 2022Review
- Checkpoint inhibitor immunotherapy diminishes oocyte number and quality in mice.Nature cancer · 2022Article
- LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade.The Journal of clinical investigation · 2022Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control. The inflamed vaccination site subsequently also sequestered and destroyed anti-CTLA-4-induced Teffs with specificities for tumor antigens other than gp100, reducing the antitumor efficacy of anti-CTLA-4 therapy. Mechanistically, Teffs at the vaccination site recruited inflammatory monocytes, which in turn attracted additional Teffs in a vicious cycle mediated by IFN-γ, CXCR3, ICAM-1, and CCL2, dependent on IFA formulation. In contrast, nonpersistent vaccine formulations based on dendritic cells, viral vectors, or water-soluble peptides potently synergized with checkpoint blockade of both CTLA-4 and PD-L1 and induced complete tumor regression, including in settings of primary resistance to dual checkpoint blockade. We conclude that cancer vaccine formulation can dominantly determine synergy, or lack thereof, with CTLA-4 and PD-L1 checkpoint blockade therapy for cancer.
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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.