Synecta™ T1 Cell-Derived Nanoparticles (CDNPs) Enable Versatile, Rapid, And Robust T Cell Expansion For Scalable CAR-T Manufacturing

By Barzan A. Sadiq, Caimei Zhang, Chiquita Hanindya, Deeksha Muthumani, Jasmine Shong, Josue Mass, Gil Joseph, Victor Carpio, Sarah Roussel, Craig Mizzoni, Sabrina Carmichael, Mojtaba Parvizi, Mosha Deng, Don Hasenmayer, Gabriela Plesa, Megan Davis, James L Riley, Peter Keller

CAR-T therapy has transformed cancer treatment, yet manufacturing remains limited by inefficient T cell activation, poor expansion, and prolonged production timelines, leading to variability, high costs, and restricted patient access. Current synthetic activators, such as beads or nanopolymers, often provide inconsistent potency and require complex handling, while feeder cells, though more effective, face safety and scalability challenges.

We have developed a novel platform using engineered artificial antigen-presenting cells to generate cell-derived nanoparticles (CDNPs) that deliver potent, physiologic T cell activation. These nanoparticles present multiple membrane-bound signaling molecules and cytokines, combining the functional advantages of feeder cells with the scalability and consistency of synthetic systems. Importantly, CDNPs can be customized to optimize T cell responses.

Our lead candidate, Synecta T1, expresses membrane-bound OKT3 scFv, CD86, 4-1BBL, IL-7, and IL-15. It drives superior T cell expansion from PBMCs, purified T cells, and patient-derived samples, supporting simultaneous Day-0 CAR transduction and activation. This enables a rapid 3-day CAR-T manufacturing process, producing robust CAR-T cells with enhanced persistence and in vivo efficacy compared with commercially available alternatives.

In preclinical studies, Synecta T1 demonstrates reproducible T cell activation across diverse patient samples and isolation methods, streamlining production while maintaining potent, physiologic stimulation. This platform represents a next-generation solution for rapid, consistent, and scalable CAR-T manufacturing.