ArticleJournal for immunotherapy of cancer2023
Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01818323 (Phase I Trial), which is not on this map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
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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 Trial: T4 Immunotherapy of Head and Neck Cancer
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The safety and efficacy of chimeric antigen receptor-T cell therapy in solid malignancies: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- CAR-T cell therapy: potential for paediatric brain tumours-an update.Journal of neuro-oncology · 2026Review
- Radiopaque microsphere-hydrogel composite for extended-release intratumoral immunotherapy in a large animal model.Drug delivery and translational research · 2026Article
- Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.Signal transduction and targeted therapy · 2026Review
- Humanized and Charge-Optimized CSPG4-Specific CAR-T Cells show Enhanced Efficacy against Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nanoparticles-enhanced CAR-T cell therapy: current advances and future directions.Biomarker research · 2026Review
- Non-Genetically Modified Adoptive Cell Therapies for Solid Tumors: Current Landscape and Future Challenges.Cancer immunology, immunotherapy : CII · 2026Review
- The Pleiotropic Roles of Cytokines in Chimeric Antigen Receptor T-cell Therapy.Cancer immunology research · 2026Review
- Sequential Release of mRNA Complex and T Cells by a Double-Layered Implantable Scaffold for Combination Therapy of Head and Neck Squamous Cell Carcinoma.International journal of nanomedicine · 2026Article
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Lentiviral-mediated panErbB CAR-T cell therapy against head and neck squamous cell carcinomas for patients with Fanconi anemia.Molecular therapy. Oncology · 2025Article
- Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.Biology · 2025Review
- Optimizing CAR T cell therapy for solid tumours: a clinical perspective.Nature reviews. Clinical oncology · 2025Review
- From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Trends in immunotherapy for oral squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Advancements and challenges in CAR-T cell therapy for solid tumors: A comprehensive review of antigen targets, strategies, and future directions.Cancer cell international · 2025Review
- CAR-T cell therapy and reconstructive oncologic surgery in peripheral solid tumors-A narrative review.Cell reports. Medicine · 2025Review
- Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.Experimental hematology & oncology · 2025Review
- CAR-Based Cell Therapy in Head and Neck Cancer: A Comprehensive Review on Clinical Applicability.Cancers · 2025Review
- Unraveling the Role of Tumor-Infiltrating Immune Cells in Head and Neck Squamous Cell Carcinoma: Implications for Antitumor Immune Responses and Immunotherapy.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
36 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundLocally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αβ, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues.
methodsWe undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1-4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×10
resultsDespite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4
conclusionsThese data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC.
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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.