On November 15, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported the publication of data demonstrating enhanced persistence of genetically modified T cells targeting leukemia through utilization of its non-viral Sleeping Beauty (SB) system to co-express membrane-bound IL-15 (mbIL15) and a CD19-specific chimeric antigen receptor (CAR) (Press release, Ziopharm, NOV 15, 2016, View Source [SID1234516794]). The article, titled "Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells," was published in the Proceedings of the National Academy of Sciences (PNAS) and is available online here.
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Using the SB system, researchers generated genetically modified T cells that preserved stem-cell memory (TSCM) by co-expressing the CAR with a fusion variant of IL-15. These engineered T cells were effective in treating established CD19+ leukemia in mice by facilitating the long-term persistence of TSCM cells sustained by signaling through mbIL15. These findings provide for a translational pipeline of immunotherapies with improved potential by combining mbIL15 and T cells with diverse specificities.
"The ability to generate CAR-T cells with preserved stem-cell memory is a novel strategy for promoting long-lived persistence and effectiveness of immunotherapies for the treatment of patients with cancers. Producing this rare, but highly desirable, T-cell subset has historically been a challenge," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM and an author of the publication.
"We have demonstrated the ability to incorporate membrane-bound IL-15 via the non-viral Sleeping Beauty platform, thereby enhancing T-cell survival and raising our expectations for corresponding therapeutic benefit. The fundamental role that IL-15 plays in T-cell activation and propagation makes it an attractive candidate to incorporate into engineered immunotherapies, and we are advancing CAR-modified T cells co-expressing mbIL15 to testing in humans," added Dr. Cooper.
The SB transposon-transposase is a unique non-viral system for introducing genes into cells and is exclusively licensed by Intrexon Corporation (NYSE:XON) through The University of Texas MD Anderson Cancer Center and accessed as part of ZIOPHARM’s collaboration with Intrexon.