Allogeneic CAR-T, CAR-NK, and in vivo CAR-T for immune-mediated inflammatory diseases: comparative evidence, platform trade-offs, and translational challenges

Immune-mediated inflammatory diseases (IMIDs) remain treatment-dependent in many patients with severe, refractory, or organ-threatening disease. Deep B-cell depletion using chimeric antigen receptor (CAR)-based therapies may induce clinical improvement and measurable immune reconstitution, but conventional autologous CAR-T manufacturing limits speed, standardization, and access. This structured narrative review compares allogeneic CAR-T, allogeneic CAR-natural killer (CAR-NK), and in vivo CAR-T. Bibliographic databases, trial registries, conference repositories, reference lists, and traceable sponsor, media, and regulatory sources were searched through 3 September 2026. Allogeneic CAR-T has the broadest clinical evidence base, although cohorts are small and mostly early-phase. All CAR-NK products with reported IMID clinical data are allogeneic; available studies suggest transient kinetics, repeat-infusion feasibility, and encouraging short-term tolerability, but durability is uncertain. Peer-reviewed in vivo evidence now includes a five-patient non-integrating LNP/linear mRNA report and a 16-patient integrating lentiviral report. Both are early, uncontrolled studies and neither supports class-wide inference. Disease-specific outcomes, background treatment, follow-up, and assays differ markedly. Complete treatment-free remission was distinguished from glucocorticoid withdrawal, immunosuppressant reduction, and remission on permitted therapy. CAR-cell, transgene DNA, and RNA detection were not pooled, and peripheral blood B-cell depletion was not treated as proof of tissue depletion. Naive-dominant B-cell recovery and declining autoantibodies indicate immune remodeling, not restored tolerance. No indirect efficacy ranking is justified. Prospective studies need standardized disease endpoints, treatment-free remission definitions, analyte-specific pharmacokinetics, paired blood–tissue pharmacodynamics, and long-term genomic, immune, and safety surveillance.