ArticleThe Journal of clinical investigation2016
Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 456 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
456 citing papers in PubMed, 662 citations in OpenAlex.
- Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.Blood cancer journal · 2024Trial
- Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma.Molecular cancer · 2023Trial
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells.Cancer immunology research · 2026Article
- Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.Signal transduction and targeted therapy · 2026Review
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- CAR-T and TIL therapies in solid tumors: barriers, clinical lessons, and convergent solutions.Cancer cell international · 2026Review
- Review
- Membrane-bound TRAIL-armoring augments CAR-T cells in mesothelin-positive solid malignancies.Journal for immunotherapy of cancer · 2026Article
- Progress in cell-based immunotherapies for solid tumors.Discover oncology · 2026Review
- Engineering programmable CAR and antigen pairing via drug-gated light activation.Nature communications · 2026Article
- Oncolytic adenoviruses encoding bispecific T cell engagers or a novel trispecific T cell engager for dual-targeting of c-MET and EGFR.Molecular therapy. Oncology · 2026Article
- Heat up and Destroy: Immunotherapy of "Cold" Tumors Using the Example of Glioblastoma.International journal of molecular sciences · 2026Review
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- CAR-T cell therapies are coming after glioblastoma: An overview of early phase clinical trials and future perspectives.iScience · 2026Review
- CAR-T cells co-expressing IL-7 and CCL19 promote epitope spreading to enhance antitumor immunity.Cancer immunology, immunotherapy : CII · 2026Article
- Article
- Therapeutic application of IL-12 for cancer therapy.Translational cancer research · 2026Review
- Dual targeting of CD155 augments the antitumor efficacy of ROR1-CAR-T cells in ovarian cancer.Cancer immunology, immunotherapy : CII · 2026Article
396 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern · 2019-07-02Concerns/Issues about Image · Investigation by Company/Institution ·
- Expression of concern
Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected to single tumor antigens. Given the heterogeneous expression of antigens on glioblastomas, we hypothesized that a bispecific CAR molecule would mitigate antigen escape and improve the antitumor activity of T cells. Here, we created a CAR that joins a HER2-binding scFv and an IL13Rα2-binding IL-13 mutein to make a tandem CAR exodomain (TanCAR) and a CD28.ζ endodomain. We determined that patient TanCAR T cells showed distinct binding to HER2 or IL13Rα2 and had the capability to lyse autologous glioblastoma. TanCAR T cells exhibited activation dynamics that were comparable to those of single CAR T cells upon encounter of HER2 or IL13Rα2. We observed that TanCARs engaged HER2 and IL13Rα2 simultaneously by inducing HER2-IL13Rα2 heterodimers, which promoted superadditive T cell activation when both antigens were encountered concurrently. TanCAR T cell activity was more sustained but not more exhaustible than that of T cells that coexpressed a HER2 CAR and an IL13Rα2 CAR, T cells with a unispecific CAR, or a pooled product. In a murine glioblastoma model, TanCAR T cells mitigated antigen escape, displayed enhanced antitumor efficacy, and improved animal survival. Thus, TanCAR T cells show therapeutic potential to improve glioblastoma control by coengaging HER2 and IL13Rα2 in an augmented, bivalent immune synapse that enhances T cell functionality and reduces antigen escape.
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.