CAR-T manufacturing reduces heterogeneity between CIDP and multiple myeloma patient-derived T cells

Rationale: CAR-T cell therapy has demonstrated remarkable promise for managing specific autoimmune disorders.However, it remains unclear, whether long-term immunosuppressive therapy in autoimmune patients adversely affects the phenotype and function of patient-derived CAR-T products.This study aimed to compare the characteristics of T cells and manufactured CAR-T cells from patients with multiple myeloma (MM) and chronic inflammatory demyelinating polyneuropathy (CIDP).Methods: T cells isolated from MM and CIDP patients, as well as healthy volunteers (for baseline comparisons only), were analyzed.CAR-T cells were generated using an identical manufacturing process.A comprehensive analysis was conducted, including flow cytometry for phenotypic and functional assessment, transcriptomic profiling via RNA sequencing, and in vitro functional assays such as cytokine secretion and cytotoxicity tests.Results: T cells from CIDP patients showed phenotypes and functional profiles more comparable to those from healthy volunteers.In contrast, MM-derived T cells showed increased CD8⁺ T cell frequency, elevated exhaustion markers, reduced naïve and less-differentiated subsets, and enhanced effector molecule production upon non-specific stimulation.CAR-T manufacturing reduced these inherent differences, yielding similar differentiation states, transcriptomic profiles, and convergent cytotoxic capacities.However, distinct immunomodulatory features persisted, as CIDP-derived CAR-T cells displayed reduced activation markers and lower IFN-γ secretion upon antigen stimulation compared to MM-derived CAR-T cells.Conclusions: Our study reveals that CAR-T manufacturing process can reduce pre-existing T-cell heterogeneity across different patient populations.These findings support the feasibility of autologous CAR-T therapies in immunosuppressed autoimmune patients, demonstrating that critical cytolytic functions are preserved despite residual alterations in cytokine profiles.