ZIOPHARM Oncology, Inc. announced improved production times utilizing its non-viral platform to engineer chimeric antigen receptor (CAR)-modified T cells in an ongoing Phase 1 study of second-generation Sleeping Beauty CD19-specific CAR+ T cells. Plans to progress the company’s point-of-care (POC) approach with administration of CAR-T cell therapy in less than 2 days are also underway helping expand access to innovative T-cell therapies. In contrast to the multi-step methods to produce virus-modified CAR- and TCR-expressing T cells, the non-viral Sleeping Beauty system offers the ability to rapidly generate genetically modified products through a simplified process. The improvements include avoiding activation and propagation of T cells as well as reduced time in culture. In the ongoing Phase 1 study utilizing second-generation Sleeping Beauty CD19-specific CAR+ T cells for lymphoid malignancies, compressed production times with younger T cells are being deployed: A patient with multiple-relapsed B-cell ALL received Sleeping Beauty-modified CD19-specific CAR+ T cells with the manufacturing time reduced to 3 weeks and achieved a complete remission with normalization of PET/CT tumor imaging. A patient with triple-hit NHL treated in January 2017 was the first to receive Sleeping Beauty-modified CD19-specific CAR+ T cells with the manufacturing time reduced to 2 weeks. In the pre-clinical setting, the time to administration of third generation Sleeping Beauty CAR+ T cells co-expressing a membrane-bound version of IL-15 (mbIL15) has been reduced to less than two days. This shortened process delivers genetically modified T cells with superior proliferative potential. Third generation Sleeping Beauty CAR+ T cells demonstrated that a single low-dose of T cells co-expressing a CD19-specific CAR and mbIL15 resulted in sustained in vivo persistence that produced potent anti-tumor effects and superior leukemia-free survival. These clinical and pre-clinical data support the company’s POC plans to rapidly infuse Sleeping Beauty CAR+ T cells in a Phase I trial to be launched later this year. With the intent to administer clinical-grade Sleeping Beauty CAR+ T cells in less than 48 hours, this non-viral CAR-T approach has the potential to outpace viral-based methods.