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Background CAR-T cell manufacturing is limited by slow production and inefficient T cell activation. Current methods introduce variability and complicate workflows while not fully addressing a variety of additional technical challenges. Rapid, robust, and consistent T cell activation technology is therefore essential for advancing CAR-T manufacturing.We developed the Synecta™ Cell-Derived Nanoparticle (CDNP) platform, which entails the surface display of membrane-bound stimulatory signals and cytokines, thus enabling more consistent, robust, and simplified CAR-T manufacturing. We hypothesized that, compared to soluble cytokines, membrane-bound formats promote more effective expansion of long-lived and highly functional T cells.Methods Three CDNP types were manufactured:Synecta T2, displaying membrane-bound OKT3 scFv, CD86, and 4-1BBL;Synecta CK1, presenting membrane-bound IL-7 and IL-15/IL-15Rα complex;Synecta T1, combining all six signals.Then, we evaluated in vitro T cell expansion, activation, and phenotype using Synecta T1 or T2 combined with Synecta CK1 or soluble cytokines.Results Synecta T1, which incorporates both membrane-bound cytokines and key T cell co-stimulatory signals, induced earlier and more robust T cell activation compared to Synecta T2, whether the latter was used alone or supplemented with soluble cytokines. T cell expansion was greater with Synecta T1, while lower expansion with Synecta T2 was partially rescued by soluble cytokine supplementation. Both Synecta T1 and T2 uniformly supported the expansion of less differentiated T cell populations, including stem cell-like and central memory phenotypes, with high expression of CD62L (>96%). Supplementing Synecta T1 with either soluble IL-7 and IL-15 or Synecta CK1 further enhanced expansion, with Synecta CK1 outperforming soluble cytokines and demonstrating a dose-sparing effect. Moreover, adding Synecta CK1 on day 6 of culture further boosted total cell yield. Finally, Synecta T1 consistently achieved higher expansion yields than synthetic activators over 3-to-9 days without the need for soluble cytokines.Conclusions Synecta™ T1 leverages membrane-bound cytokines to achieve robust T cell activation and expansion without utilizing soluble cytokines. Its performance may be partly due to the presence of membrane-bound IL-15Rα, which needs to be complexed with IL-15 on the cell surface to promote cell activation. Synecta™ T2 provides a modular and highly adaptable platform that enables fine-tuning of activation by combining with soluble or membrane-bound cytokines. This flexibility makes Synecta T2 particularly well-suited for tailoring stimulation protocols to diverse cell types, patient populations, or manufacturing needs. Ongoing studies aim to optimize dosing and regimens and will further explore the integration of IL-2 and other cytokines.