ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 255 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
255 citing papers in PubMed, 1 synthesis or guideline pooled it, 368 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma.Journal of translational medicine · 2025Trial
- Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma.Molecular cancer · 2023Trial
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Co-expression of non-signaling CARs enhances EGFRvIII-specific CAR T-cell cytotoxicity against head and neck squamous cell carcinoma.BMC cancer · 2026Article
- FOXP1 Knockdown Reprograms Th9 CAR-T Cells to Overcome Antigen Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bispecific CAR T and CAR NK cells in dual-threat immunotherapy: opportunities and challenges.Molecular biology reports · 2026Review
- Dual CAR-NK cells targeting PD-L1 and ErbB2 (HER2) exhibit cooperative CAR signaling and counteract solid tumor heterogeneity.Journal of experimental & clinical cancer research : CR · 2026Article
- Bridging biomaterials and immunotherapy: hydrogel strategies for next-generation CAR-T cell treatment.Stem cell research & therapy · 2026Review
- Immunotheranostics in Solid Tumors: Longitudinal Tracking of Human IL13Rα2 CAR-T Cells In Vivo.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 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
- Safety and clinical outcomes of a first-in-human trial of point-of-care manufactured trispecific CAR T cells targeting CD19, CD20, and CD22.Research square · 2026Article
- Mathematical modeling of combinatorial antigen targeting with multiple CAR T-cell products for glioblastoma treatment.NPJ systems biology and applications · 2026Article
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Multi-antigen chimeric antigen receptor-T cell therapy for relapsed/refractory B cell lymphomas.Frontiers in immunology · 2026Review
- The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.Frontiers in immunology · 2026Review
- Chimeric antigen receptor macrophages therapy for glioblastoma: challenges and opportunities from preclinical evidence to clinical translation.Frontiers in immunology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- Optimal pairing of binder and co-stimulatory domains improves dual CART cell efficacy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Computational structural optimization enhances IL13Rα2 - B7-H3 tandem CAR T cells to overcome antigen-heterogeneity-mediated tumor escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
195 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedGottachalk, Stephen [corrected to Gottschalk, Stephen]
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed that targeting HER2 in a glioblastoma (GBM) cell line results in the emergence of HER2-null tumor cells that maintain the expression of nontargeted tumor-associated antigens. Combinational targeting of these tumor-associated antigens could therefore offset this escape mechanism. We studied the single-cell coexpression patterns of HER2, IL-13Rα2, and EphA2 in primary GBM samples using multicolor flow cytometry and immunofluorescence, and applied a binomial routine to the permutations of antigen expression and the related odds of complete tumor elimination. This mathematical model demonstrated that cotargeting HER2 and IL-13Rα2 could maximally expand the therapeutic reach of the T cell product in all primary tumors studied. Targeting a third antigen did not predict an added advantage in the tumor cohort studied. We therefore generated bispecific T cell products from healthy donors and from GBM patients by pooling T cells individually expressing HER2 and IL-13Rα2-specific CARs and by making individual T cells to coexpress both molecules. Both HER2/IL-13Rα2-bispecific T cell products offset antigen escape, producing enhanced effector activity in vitro immunoassays (against autologous glioma cells in the case of GBM patient products) and in an orthotopic xenogeneic murine model. Further, T cells coexpressing HER2 and IL-13Rα2-CARs exhibited accentuated yet antigen-dependent downstream signaling and a particularly enhanced antitumor activity.
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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.