ArticleThe Journal of clinical investigation2022
An optimized bicistronic chimeric antigen receptor against GPC2 or CD276 overcomes heterogeneous expression in neuroblastoma.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 66 citations in OpenAlex.
- A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- CAR-T cell therapy for pediatric solid tumors: armored CAR-T cells and beyond.Cancer metastasis reviews · 2026Review
- Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- GPC2-CAR T cells have potent preclinical activity against orthotopic medulloblastoma xenografts.Molecular therapy. Oncology · 2025Article
- B7-H3 in the tumor microenvironment: Implications for CAR T cell therapy in pediatric solid tumors.Cancer metastasis reviews · 2025Review
- B7-H3 in the tumor microenvironment: Implications for CAR T cell therapy in pediatric solid tumors.Cancer metastasis reviews · 2025Review
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- Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer.NPJ precision oncology · 2025Article
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- ImmunoTar-integrative prioritization of cell surface targets for cancer immunotherapy.Bioinformatics (Oxford, England) · 2025Article
- Challenges and overcoming strategies in CAR-T cell therapy for pediatric neuroblastoma.World journal of pediatrics : WJP · 2025Article
- Inferring disease progression stages in single-cell transcriptomics using a weakly supervised deep learning approach.Genome research · 2025Article
- Genetic Risk Profiling Reveals Altered Glycosyltransferase Expression as a Predictor for Patient Outcome in Neuroblastoma.Journal of clinical medicine · 2025Article
- In-depth analysis of the safety of CAR-T cell therapy for solid tumors.Frontiers in immunology · 2025Review
- Developing CAR T-Cell Therapies for Pediatric Solid Tumors.Paediatric drugs · 2025Review
- CAR T-cells for pediatric solid tumors: where to go from here?Cancer metastasis reviews · 2024Review
- Advances in Immunomodulatory Mesoporous Silica Nanoparticles for Inflammatory and Cancer Therapies.Biomolecules · 2024Review
- CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma.Nature communications · 2024Article
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23 authors at 5 institutions in 2 countries.
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Abstract
Chimeric antigen receptor (CAR) T cell therapies targeting single antigens have performed poorly in clinical trials for solid tumors due to heterogenous expression of tumor-associated antigens (TAAs), limited T cell persistence, and T cell exhaustion. Here, we aimed to identify optimal CARs against glypican 2 (GPC2) or CD276 (B7-H3), which were highly but heterogeneously expressed in neuroblastoma (NB), a lethal extracranial solid tumor of childhood. First, we examined CAR T cell expansion in the presence of targets by digital droplet PCR. Next, using pooled competitive optimization of CAR by cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq), termed P-COCC, we simultaneously analyzed protein and transcriptome expression of CAR T cells to identify high-activity CARs. Finally, we performed cytotoxicity assays to identify the most effective CAR against each target and combined the CARs into a bicistronic "OR" CAR (BiCisCAR). BiCisCAR T cells effectively eliminated tumor cells expressing GPC2 or CD276. Furthermore, the BiCisCAR T cells demonstrated prolonged persistence and resistance to exhaustion when compared with CARs targeting a single antigen. This study illustrated that targeting multiple TAAs with BiCisCAR may overcome heterogenous expression of target antigens in solid tumors and identified a potent, clinically relevant CAR against NB. Moreover, our multimodal approach integrating competitive expansion, P-COCC, and cytotoxicity assays is an effective strategy to identify potent CARs among a pool of candidates.
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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.