ArticleBreast cancer research and treatment2021
Fourth-generation chimeric antigen receptor T cells targeting folate receptor alpha antigen expressed on breast cancer cells for adoptive T cell therapy.
Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Investigating the role of costimulatory domains in enhancing CAR-T cell persistence in TNBC.Cancer gene therapy · 2026Review
- Microfluidic Cytotongue system enables early, label-free detection of CAR-T-induced mechanical softening in tumor spheroids.Microsystems & nanoengineering · 2026Article
- Dual Targeting of FAP-Directed Nanoparticles and FRα-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer.International journal of biological sciences · 2026Article
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- The potential of chimeric antigen receptor -T cell therapy for endocrine cancer.World journal of surgical oncology · 2025Review
- From spheroids to organoids: next-generation models for CAR-T cell therapy research in solid tumors.Frontiers in immunology · 2025Review
- Article
- CRISPR/Cas9-mediated knockout strategies for enhancing immunotherapy in breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- CAR T cell infiltration and cytotoxic killing within the core of 3D breast cancer spheroids under the control of antigen sensing in microwell arrays.APL bioengineering · 2024Article
- Immunologic tumor microenvironment modulators for turning cold tumors hot.Cancer communications (London, England) · 2024Review
- The nexus of natural killer cells and melanoma tumor microenvironment: crosstalk, chemotherapeutic potential, and innovative NK cell-based therapeutic strategies.Cancer cell international · 2023Review
- Review
- Review
- Enhancement of PD-L1-attenuated CAR-T cell function through breast cancer-associated fibroblasts-derived IL-6 signaling via STAT3/AKT pathways.Breast cancer research : BCR · 2023Article
- Fine-Tuning through Generations: Advances in Structure and Production of CAR-T Therapy.Cancers · 2023Review
- Review
- Chimeric Antigen Receptor T-Cell Therapy for Solid Tumors: The Past and the Future.Journal of immunotherapy and precision oncology · 2023Review
- Сytotoxic effect of CAR-T cells against modified MCF-7 breast cancer cell line.Molecular biology research communications · 2023Article
- Immunotherapy and immunoengineering for breast cancer; a comprehensive insight into CAR-T cell therapy advancements, challenges and prospects.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- The challenge of selecting tumor antigens for chimeric antigen receptor T-cell therapy in ovarian cancer.Medical oncology (Northwood, London, England) · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
purposeTreatment of breast cancer (BC) by standard methods is effective in the early stage, but ineffective in the advanced stage of disease. To develop an adoptive T cell therapy for advanced and severe BC, we generated fourth-generation chimeric antigen receptor (CAR) T cells targeting folate receptor alpha antigen (FRα) expressed on BC cells, and preclinically evaluated their anti-BC activities.
methodsThe fourth-generation FRα-CAR T cells containing extracellular FRα-specific single-chain variable fragment (scFv) and three intracellular costimulatory domains (CD28, 4-1BB, and CD27) linked to CD3ζ were generated using a lentiviral system, and then were evaluated for their anti-BC activities in two-dimensional and three-dimensional (spheroid) cultures.
resultsWhen our fourth-generation FRα-CAR T cells were cocultured with FRα-expressing MDA-MB-231 BC cell line at an effector to target ratio of 20:1, these CAR T cells specifically lysed 88.7 ± 10.6% of the target cells. Interestingly, the cytotoxic lysis of FRα-CAR T cells was more pronounced in target cells with higher surface FRα expression. This specific cytotoxicity of the CAR T cells was not observed when cocultured with FRα-negative MCF10A normal breast-like cell line at the same ratio (34.3 ± 4.7%). When they were cocultured with MDA-MD-231 spheroid, the FRα-CAR T cells exhibited antitumor activity marked with spheroid size reduction and breakage.
conclusionThis proof-of-concept study thus shows the feasibility of using these fourth-generation FRα-CAR T cells for adoptive T cell therapy in BC.
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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.