ArticleJournal for immunotherapy of cancer2025
CD22 CAR-T cells secreting CD19 T-cell engagers for improved control of B-cell acute lymphoblastic leukemia progression.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Comparative clinical outcomes and single-cell profiling of CD19 CAR-T versus blinatumomab for relapsed/refractory B-ALL.Journal for immunotherapy of cancer · 2026Article
- A roadmap for systematic humanization of a chimeric antigen receptor: preclinical validation of a humanized CD22 scFv as a model.Experimental hematology · 2026Article
- Advancements in diagnosis and treatments of acute leukemia.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Optimizing the Efficacy-Toxicity Paradigm in Pediatric Oncology: A Narrative Review of Immunotherapy and Survivorship Outcomes.Current oncology (Toronto, Ont.) · 2026Review
- 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
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- Review
- mRNA-engineered T lymphocytes secreting bispecific T cell engagers with therapeutic potential in solid tumors.Frontiers in immunology · 2025Article
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCD19-directed cancer immunotherapies, based on engineered T cells bearing chimeric antigen receptors (CARs, CAR-T cells) or the systemic administration of bispecific T cell-engaging (TCE) antibodies, have shown impressive clinical responses in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, more than half of patients relapse after CAR-T or TCE therapy, with antigen escape or lineage switching accounting for one-third of disease recurrences. To minimize tumor escape, dual-targeting CAR-T cell therapies simultaneously targeting CD19 and CD22 have been developed and validated both preclinically and clinically.
methodsWe have generated the first dual-targeting strategy for B-cell malignancies based on CD22 CAR-T cells secreting an anti-CD19 TCE antibody (CAR-STAb-T) and conducted a comprehensive preclinical characterization comparing its therapeutic potential in B-ALL with that of previously validated dual-targeting CD19/CD22 tandem CAR cells (TanCAR-T cells) and co-administration of two single-targeting CD19 and CD22 CAR-T cells (pooled CAR-T cells).
resultsWe demonstrate that CAR-STAb-T cells efficiently redirect bystander T cells, resulting in higher cytotoxicity of B-ALL cells than dual-targeting CAR-T cells at limiting effector:target ratios. Furthermore, when antigen loss was replicated in a heterogeneous B-ALL cell model, CAR-STAb T cells induced more potent and effective cytotoxic responses than dual-targeting CAR-T cells in both short- and long-term co-culture assays, reducing the risk of CD19-positive leukemia escape. In vivo, CAR-STAb-T cells also controlled leukemia progression more efficiently than dual-targeting CAR-T cells in patient-derived xenograft mouse models under T cell-limiting conditions.
conclusionsCD22 CAR-T cells secreting CD19 T-cell engagers show an enhanced control of B-ALL progression compared with CD19/CD22 dual CAR-based therapies, supporting their potential for clinical testing.
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