ReviewFrontiers in immunology2026
Resistance mechanisms and translational bottlenecks in CAR-T cell therapy for pediatric acute lymphoblastic leukemia: a perspective.
Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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Abstract
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable remission rates exceeding 80% in relapsed/refractory pediatric B-cell acute lymphoblastic leukemia (B-ALL), yet 40-50% of patients eventually relapse within the first year. This therapeutic ceiling is not a single failure mode but the convergence of at least four interrelated layers: loss of CAR-T persistence, antigen escape driven by CD19 splicing variants and lineage switch, CAR-T cell-intrinsic exhaustion from chronic tonic signaling, and an immunosuppressive bone marrow microenvironment that actively extinguishes effector function. Our systematic analysis of 226 pediatric-eligible CAR-T trials shows that 95.6% are Phase I-II, 3.5% (8/226) are registered as Phase III/IV, and 58 of 102 completed trials (56.9%) had no outcome recorded in the source database. In this Perspective, we synthesize the molecular mechanisms of CAR-T resistance, contextualize them within the current clinical trial landscape, and critically evaluate emerging engineering strategies-from dual-targeting and armored CAR architectures to CRISPR-edited allogeneic products and
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