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Accelerating clinical scale production of BCMA CAR T cells with defined maturation stages

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Item Type:Article
Title:Accelerating clinical scale production of BCMA CAR T cells with defined maturation stages
Creators Name:Joedicke, J.J. and Großkinsky, U. and Gerlach, K. and Künkele, A. and Höpken, U.E. and Rehm, A.
Abstract:The advent of CAR T cells targeting CD19 or BCMA on B cell neoplasm demonstrated remarkable efficacy, but rapid relapses or primary refractoriness remains challenging. A leading cause for CAR T cell failure is their lack of expansion and limited persistence. Long-lived, self-renewing multipotent T memory stem cells (T(SCM)) and T central memory cells (T(CM)) likely sustain superior tumor regression, but their low frequencies in blood from cancer patients imposes a major hurdle for clinical CAR T production. We designed a clinically compliant protocol for generating BCMA CAR T cells starting with increased T(SCM)/T(CM) cell input. A CliniMACS Prodigy process was combined with flow cytometry-based enrichment of CD62L(+)CD95(+) T cells. Although starting with only 15% of standard T cell input, the selected T(SCM)/T(CM) material was efficiently activated and transduced with a BCMA CAR-encoding retrovirus. Cultivation in the presence of IL-7/IL-15 enabled the harvest of CAR T cells containing an increased CD4(+) T(SCM) fraction and 70% CD8(+) T(SCM) cells. Strong cell proliferation yielded cell numbers sufficient for clinical application, while effector functions were maintained. Together, adaptation of a standard CliniMACS Prodigy protocol to low input numbers resulted in efficient retroviral transduction with a high CAR T cell yield.
Keywords:Chimeric Antigen Receptor T Cell, T Central Memory Cell, T Memory Stem Cell, GMP Manufacturing, Prodigy Bioreactor, Adoptive T Cell Therapy, Flow Cytometry Cell Sorting, Retrovirus
Source:Molecular Therapy - Methods and Clinical Development
Publisher:Cell Press
Page Range:181-198
Date:10 March 2022
Official Publication:https://doi.org/10.1016/j.omtm.2021.12.005
PubMed:View item in PubMed

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