Trial reportProceedings of the National Academy of Sciences of the United States of America2008
Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 326 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase I Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases
A Correlative Study of Melanoma Tumor-Infiltrating Lymphocytes (TILs) and Response to Ipilimumab
A Phase II Trial of GM-CSF Plus Maintenance Pembrolizumab +/- Pemetrexed After Completion of First Line Chemo-Immunotherapy in Advanced Non-Small Cell Lung Cancer Patients with PDL-1 of 1%-49%
Who cites it
326 citing papers in PubMed, 5 syntheses or guidelines pooled it, 648 citations in OpenAlex.
- Tumor infiltrating lymphocytes as an endpoint in cancer vaccine trials.Frontiers in immunology · 2023Pooled it
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma.Journal for immunotherapy of cancer · 2022Guideline
- Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.Frontiers in medicine · 2020Pooled it
- Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor-induced colitis.Alimentary pharmacology & therapeutics · 2019Pooled it
- Defining the Most Appropriate Primary End Point in Phase 2 Trials of Immune Checkpoint Inhibitors for Advanced Solid Cancers: A Systematic Review and Meta-analysis.JAMA oncology · 2018Pooled it
- Randomized phase II trial of nivolumab and ipilimumab with or without stereotactic body radiation therapy in patients with metastatic castration-resistant prostate cancer: the CheckPRO, CA209-8TY trial.Journal for immunotherapy of cancer · 2026Trial
- Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy.Frontiers in immunology · 2020Trial
- The role of interimEuropean journal of nuclear medicine and molecular imaging · 2018Trial
- Absolute number of new lesions onEuropean journal of nuclear medicine and molecular imaging · 2018Trial
- Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma-safety and efficacy in a phase II study.Cancer immunology, immunotherapy : CII · 2017Trial
- Trial
- Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2026Review
- Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).International journal of molecular medicine · 2026Review
- Nanobody-based bispecific antibody engagers targeting CTLA-4 or PD-L1 for cancer immunotherapy.Nature biomedical engineering · 2026Article
- Combination immunotherapy in hepatocellular carcinoma: synergies among immune checkpoints, TKIs, and chemotherapy.Journal of hematology & oncology · 2025Review
- Review
- The dynamic immune behavior of primary and metastatic ovarian carcinoma.NPJ precision oncology · 2025Article
- Plasticity of tumor cell immunogenicity: is it druggable?Journal for immunotherapy of cancer · 2025Article
- Neoadjuvant immune checkpoint therapy: Enabling insights into fundamental human immunology and clinical benefit.Cancer cell · 2025Review
- Intratumoral administration of mRNA COVID-19 vaccine delays melanoma growth in mice.Scientific reports · 2025Article
266 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 8 institutions in 1 country.
Funding
Abstract
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration of fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, patients that respond also frequently manifest serious inflammatory pathologies, raising the possibility that the therapeutic and toxic effects of CTLA-4 blockade might be linked. Here we show that periodic infusions of anti-CTLA-4 antibodies after vaccination with irradiated, autologous tumor cells engineered to secrete GM-CSF (GVAX) generate clinically meaningful antitumor immunity without grade 3 or 4 toxicity in a majority of metastatic melanoma patients. The application of this sequential immunotherapy to advanced ovarian carcinoma patients also revealed that tumor destruction and severe inflammatory pathology could be dissociated, although further refinements are required to increase clinical responses and to minimize toxicity in this population. The extent of therapy-induced tumor necrosis was linearly related to the natural logarithm of the ratio of intratumoral CD8(+) effector T cells to FoxP3(+) regulatory T cells (Tregs) in posttreatment biopsies. Together, these findings help clarify the immunologic and clinical effects of CTLA-4 antibody blockade in previously vaccinated patients and raise the possibility that selective targeting of antitumor Tregs may constitute a complementary strategy for combination therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.