ArticleCancer immunology research2021
Bispecific CAR T Cells against EpCAM and Inducible ICAM-1 Overcome Antigen Heterogeneity and Generate Superior Antitumor Responses.
Article in Cancer immunology research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 55 citations in OpenAlex.
- Extracellular matrix-targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors.Science advances · 2026Article
- ICAM1-targeted costimulation extends HER2 CAR T cytotoxicity to HER2-low and HER2-negative tumors through synergy with TCR signaling.Molecular therapy. Oncology · 2026Article
- Integrated RNA Sequencing and Multi-Bioinformatics Analyses Reveal the Molecular Mechanisms Underlying the Anti-Breast Cancer Effects of the Fritillariae Thunbergii Bulbus-Bolbostemmatis Rhizoma Herb Pair.Cell biochemistry and function · 2026Article
- CAR-T cell therapy for pancreatic cancer: Translating emerging targets and dual-targeting strategies from solid tumors.Frontiers in immunology · 2026Review
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- Preclinical evaluation of CAR-T cell immunotherapy with a fully human EpCAM-specific scFv against pancreatic cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Dual implication of endothelial adhesion molecules in tumor progression and cancer immunity.Cell adhesion & migration · 2025Review
- Barriers and solutions for CAR-T therapy in solid tumors.Cancer gene therapy · 2025Review
- P-21 Kinase 1 or 4 Knockout Stimulated Anti-Tumour Immunity Against Pancreatic Cancer by Enhancing Vascular Normalisation.International journal of molecular sciences · 2025Article
- [CAR T cells in solid tumors: resistance mechanisms].Innere Medizin (Heidelberg, Germany) · 2025Review
- Resistance Mechanisms to BCMA Targeting Bispecific Antibodies and CAR T-Cell Therapies in Multiple Myeloma.Cells · 2025Review
- New approaches of chimeric antigen receptor (CAR)-immune cell-based therapy in gastric cancer; highlight CAR-T and CAR-NK.Functional & integrative genomics · 2025Review
- CV1-secreting sCAR-T cells potentiate the abscopal effect of microwave ablation in heterogeneous tumors.Cell reports. Medicine · 2025Article
- EpCAM Signaling in Oral Cancer Stem Cells: Implications for Metastasis, Tumorigenicity, and Therapeutic Strategies.Current issues in molecular biology · 2025Review
- Mechanisms, advances, and challenges of immunotherapy in gastric cancer.Frontiers in immunology · 2025Review
- Reshaping CAR-T cells through overexpression of T cell factor 1.Frontiers in immunology · 2025Article
- ImmunoPET imaging of EpCAM in solid tumours with nanobody tracers: a preclinical study.European journal of nuclear medicine and molecular imaging · 2025Article
- Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies.Journal of immunology research · 2025Review
- CAR-T cell therapy: Advances in digestive system malignant tumors.Molecular therapy. Oncology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated unparalleled responses in hematologic cancers, yet antigen escape and tumor relapse occur frequently. CAR T-cell therapy for patients with solid tumors faces even greater challenges due to the immunosuppressive tumor environment and antigen heterogeneity. Here, we developed a bispecific CAR to simultaneously target epithelial cell adhesion molecule (EpCAM) and intercellular adhesion molecule 1 (ICAM-1) to overcome antigen escape and to improve the durability of tumor responses. ICAM-1 is an adhesion molecule inducible by inflammatory cytokines and elevated in many types of tumors. Our study demonstrates superior efficacy of bispecific CAR T cells compared with CAR T cells targeting a single primary antigen. Bispecific CAR T achieved more durable antitumor responses in tumor models with either homogenous or heterogenous expression of EpCAM. We also showed that the activation of CAR T cells against EpCAM in tumors led to upregulation of ICAM-1, which rendered tumors more susceptible to ICAM-1 targeting by bispecific CAR T cells. Our strategy of additional targeting of ICAM-1 may have broad applications in augmenting the activity of CAR T cells against primary tumor antigens that are prone to antigen loss or downregulation.
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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.