Rapid cell expansion (RACE) technology for production of engineered autologous T-cell therapy: Path toward manageable multicenter clinical trials in aggressive NHL with anti-CD19 CAR.

3079 Background: Engineered autologous T cell therapy is proving to be a promising method to treat a variety of tumor types. An ongoing National Cancer Institute (NCI) Phase 1/2a study in patients with refractory B cell malignancies has been particularly encouraging, with data presented most recently at the ASH 2013 annual meeting. To prepare for Kite-sponsored multicenter trials, a rapid and compliant manufacturing process has been developed. Because refractory B cell malignancies can progress quickly, it is important to reduce the time between apheresis of patient PBMCs and administration of the engineered T cells. Methods: PBMCs from normal donors and patients with B cell malignancies were stimulated in vitro with anti-CD3 antibody in the presence of IL-2 to initiate T cell growth. The cells were then transduced with a gamma-retroviral vector containing an anti-CD19 CAR gene and propagated in culture to generate sufficient engineered T cells for administration. Results: We have developed a 6-day manufacturing process in serum-free media without the use of CD3/CD28 beads. Development studies have demonstrated in vitro analytical comparability to cells produced using an open system at the NCI. Conclusions: Kite in conjunction with the NCI Surgery Branch has developed a rapid and efficient proprietary process for the generation of anti-CD19 CAR cells. A Kite-sponsored multicenter clinical trial in patients with aggressive non-Hodgkin lymphoma using T cells generated by this new manufacturing process is expected to begin in early 2015.