Ziopharm Planning Phase 1 Trial of CAR T-cells Produced in Less Than 2 Days

Ziopharm Planning Phase 1 Trial of CAR T-cells Produced in Less Than 2 Days

Modifying T-cells to recognize specific cancer proteins has shown promise in a number of trials, but the manufacturing times are often a limitation of such approaches. Now, Ziopharm Oncology is hoping to change that.

Ziopharm is working to take CAR T-cells into patients in less than 48 hours, which will help expand access to these T-cell therapies. The company is collaborating with Intrexon and the MD Anderson Cancer Center in its immuno-oncology program.

Compared to the multistep approaches that use viral vectors to modify CAR- and TCR-expressing T-cells, Ziopharm uses a non-viral system, called Sleeping Beauty, which allows these cells to be generated through a simplified process that reduces time in culture and T-cell activation before injection into the patient.

“Through the application of Intrexon’s industrial engineering components and principles, we have enhanced our non-viral approach to T-cell therapies,” Laurence Cooper, MD, PhD, CEO of Ziopharm, said in a press release.

“Shortening the manufacturing process and avoiding the complexity of viral-based approaches with Sleeping Beauty represents a significant advance which dramatically reduces barriers to broadening delivery of CAR-expressing T-cells to a wide range of institutions and, importantly, cancer patients in need,” Cooper said.

The first-generation Sleeping Beauty was tested in two Phase 1 trials (NCT00968760 and NCT01497184). The CD19-specific CAR T-cells were manufactured in four weeks and provided long-term survival in patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma.

Ziopharm is currently using the second-generation Sleeping Beauty CD19 CAR T-cells in an ongoing Phase 1 trial (NCT01492036) which is still recruiting participants. These cells are being produced faster than those using the first-generation system.

In one patient with relapsed B-cell ALL, researchers managed to produce CD19 CAR T-cells within three weeks. The patient achieved complete remission as assessed through PET/CT scans.

Researchers reduced the manufacturing time to two weeks in a patient with non-Hodgkin’s lymphoma. This patient was treated in January 2017, and was the first to receive CAR T-cells that had been manufactured within two weeks.

The company is now working on third-generation Sleeping Beauty CAR T-cells that express a membrane-bound IL-15 molecule. In preclinical trials, the manufacturing process of these cells was reduced to less than two days, allowing the delivery of T-cells with higher proliferative potential.

The results were presented at the 58th American Society of Hematology (ASH) Annual Meeting in December 2016, and the company is planning to use these cells in a Phase 1 trial to be launched in late 2017.

“Our ability to generate T-cells that co-express immunoreceptors and cytokines such as membrane-bound IL-15 through non-viral gene transfer, plus integration of our RheoSwitch Therapeutic System enabling conditional control of these and other essential components, represents what we believe will be the best-in-class platform in CAR-T and TCR-based cellular therapy,” said Geno Germano, president of Intrexon.

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