ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T-cell-dependent tumor eradication and decreases risk of toxic side effects.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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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.
A Phase I/II Clinical Trial on the Per-operative Intratumoral Administration of Myeloid Dendritic Cells Plus Ipilimumab and Nivolumab, Followed by Repeated Intracavitary Plus Intravenous Administration of Nivolumab in Patients With Recurrent Glioblastoma
Phase I-II Study of Intratumoral Urelumab Combined With Nivolumab in Patients With Solid Tumors
Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 192 citations in OpenAlex.
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- Translating a Preclinical Hydrogel Platform into a Human Therapeutic for Delivering Targeted Low-Dose Anti-CTLA-4.Gels (Basel, Switzerland) · 2026Article
- Local immunotherapy in the neoadjuvant treatment of cancer: optimizing efficacy while limiting toxicity?Journal for immunotherapy of cancer · 2026Review
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- Impact of tumor localization on antitumor immunity with conditionally activated CTLA-4 blockade.Journal for immunotherapy of cancer · 2025Article
- Future perspectives on immunotherapy for hepatocellular carcinoma.Therapeutic advances in medical oncology · 2025Review
- Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma.Neuro-oncology · 2024Article
- A platform technology for ultra-long acting intratumoral therapy.Scientific reports · 2024Article
- A large-scale machine learning analysis of inorganic nanoparticles in preclinical cancer research.Nature nanotechnology · 2024Article
- Peritumoral administration of immunomodulatory antibodies as a triple combination suppresses skin tumor growth without systemic toxicity.Journal for immunotherapy of cancer · 2024Article
- Tumor-draining lymph nodes: opportunities, challenges, and future directions in colorectal cancer immunotherapy.Journal for immunotherapy of cancer · 2024Review
- Targeting tumor-infiltrating tregs for improved antitumor responses.Frontiers in immunology · 2024Review
- Comparative analysis of diagnostic ultrasound and histopathology for detecting cervical lymph node metastases in head and neck cancer.Journal of cancer research and clinical oncology · 2023Article
- Immunotherapeutic Agents for Intratumoral Immunotherapy.Vaccines · 2023Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeBlockade of CTLA-4 by antibodies has potentiated antitumor T-cell responses in both preclinical models and clinical trials. However, treatment with CTLA-4 blocking antibodies is associated with autoimmune and inflammatory side effects. In this study, we propose a novel administration method for CTLA-4 blocking antibodies as monotherapy. EXPERIMENTAL
designWe use different preclinical mouse models of cancer to investigate the local administration of CTLA-4 blocking antibody and its effect on cancer progression and the antitumor T-cell response.
resultsBy injecting the antibodies in a subcutaneous slow-release delivery formulation in the tumor area, we show that an eight-fold lower dose of antibody is as effective in inducing tumor eradication as systemic delivery. A lower dose and slow release of the antibody results in thousand-fold decreased levels of antibody in the serum, reducing adverse events and the risk of autoimmunity. The main target and effector cells of the CTLA-4 blockade treatment in the studied tumor models are tumor-specific endogenous CD8(+) T cells that are capable of eradicating also distant tumors, whereas CD4(+) T cells do not play a prominent role in the antibody-mediated tumor eradication.
conclusionsInjecting CTLA-4 blocking antibody in a slow-release formulation close to the tumor is an effective way of activating the antitumor T-cell response. This administration method is associated with very low serum levels of antibody, which decreases the risk of treatment-induced side effects. These results call for exploration of a similar delivery principle in clinical settings.
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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.