JUNO Therapeutics announced that it hopes to accelerate its process for developing chimeric antigen receptor (CAR) T cells from weeks to just 2 days.
The Seattle-based company bought Stage Cell Therapeutics GmbH in May 2015 looking to incorporate the German biotech firm’s automated manufacturing process and cell selection and activation capabilities with its existing cellular therapy pipeline.
During a conference call with investors on May 5, Juno CEO Hans Bishop said that technology and processes gained with Stage Cell are allowing Juno to speed up its T cell manufacturing process.
“We’re actively working on a completely new set of manufacturing technologies that have the potential to generate CAR T cells in around 2 days,” Bishop said. “We continue to make solid progress with those technologies.
“It’s a 2-part system; 1 relies on a new automated instrument and the other relies on some novel reagents that work specifically with that instrument. A number of the technical hurdles, particularly around the reagents, we’re making good progress on. We continue to be encouraged with the application and the potential of that technology.”
He added that the company is still considering ways to optimize the manufacturing process.
“We believe the type of CAR T cell matters and we have invested significantly in the manufacturing technologies needed to control the type of cell in the final product,” Bishop said. “We remain optimistic that this will be a source of competitive advantage. To that end, we continue to focus on executing our potential best-in-class program, JCAR017, which uses our defined-cell technology.”
Producing these cells remains an ongoing challenge, and both pharmaceutical companies and device manufacturers are working to find a way to speed up and automate the process. As noted in a 2015 paper by Kaiser et al published in Cancer Gene Therapy
, manufacturing CAR T cells is labor-intensive, involves several steps, and the failure rate can be high.1
The process starts with collecting peripheral blood mononuclear cells (PBMC) from the patient, enriching and activating those PBMCs for T cells prior to gene modification, multiplying those T cells to the required dose levels, then reinfusion into the patient. The cell product must be evaluated with several quality control assays, and must meet all release criteria and Good Manufacturing Practices guidelines.
“Moreover, dedicated infrastructure with clean rooms and all required instruments must be in place, qualified, and functional to ensure aseptic and sterile containment,” Kaiser et al wrote.
Scaling up production for commercial use requires (1) a manufacturing process that results in a safe and clinically effective cell product for the patient and (2) the process must be “robustly reproducible,” which to be validated and to ensure quality during the entire product life-cycle.
“These requirements, especially with regard to process, can only be partially met in the currently available clinical manufacturing processes of therapeutic cell products,” researchers wrote.
In phase I results presented at the 2017 ASH Annual Meeting, Juno’s CAR T-cell therapy JCAR017 induced an objective response rate of 80%, including a complete response rate of 60% in patients with relapsed or refractory CD19-positive non-Hodgkin lymphoma.2
Forty-two percent of assessable patients remained in response after 3 months of follow-up.
Bishop said the company will present updated data from the trial in diffuse large B-cell lymphoma at ASCO in June. Juno plans to initiate a pivotal trial this fall.
The FDA granted breakthrough therapy designation to JCAR017 for relapsed/refractory, aggressive large B-cell non-Hodgkin lymphoma in December 2016. Breakthrough therapy designation is meant to expedite the development of promising medications that have shown preliminary signs of clinical efficacy, typically in phase I or II trials. Under the program, the FDA provides advice on the design and conduct of the clinical development program.
- Kaiser AD, Assenmacher M, Schröder B, et al. Towards a commercial process for the manufacture of genetically modified T cells for therapy. Cancer Gene Ther. 2015;22:72-78.
- Abramson JS, Palomba L, Gordon LI, et al. Transcend NHL 001: Immunotherapy with the CD19-Directed CAR T-Cell Product JCAR017 Results in High Complete Response Rates in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma. Presented at: 58th American Society of Hematology Annual Meeting; San Diego, CA; December 3-6, 2016. Abstract 4192.