By Claire Coeshott, Boah Vang, Mark Jones and Brian Nankervis
There have been remarkable recent advances in cellular immunotherapies to treat cancer, in particular in the expansion and use of gene-modified T-cells, expressing chimeric antigen receptors (CARs), for the treatment of advanced hematologic cancers. Recent U.S. Food and Drug Administration (FDA) approvals of tisagenlecleucel, which targets B-cell acute lymphoblastic leukemia (B-ALL) and relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL), and of axicabtagene ciloleucel (axi-cel) , which targets r/r DLBCL, are evidence of the promise of these approaches for the future treatment of cancer. These cellular therapies require the manufacture of up to billions of autologous T-cells for re-infusion to the patient and thus technologies that can address the labor intensity, costs and requirements for Good Manufacturing Practice (GMP) to achieve these cell numbers are being sought.
The rapid evolution of cell-based immunotherapies such as chimeric antigen receptor T-cells for treatment of hematological cancers has precipitated the need for a platform to expand these cells ex vivo in a safe, efficient, and reproducible manner.
In this report, we demonstrate that the Quantum system is a versatile platform for the manufacture of T-cells that retain functionality and that display phenotypes of relevance for cancer immunotherapy. Moreover, we show that this can be done at a large scale, consistently generating billions of CD3+ T-cells in a short timeframe, while providing the potential for significant reduction of labor and expense through automated programming and unique dual-loop circuits.
Coeshott, C., Vang, B., Jones, M. et al. Large-scale expansion and characterization of CD3+ T-cells in the Quantum® Cell Expansion System. J Transl Med 17, 258 (2019). https://doi.org/10.1186/s12967-019-2001-5