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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., Großkinsky, U., Gerlach, K., Künkele, A., 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 |
| ISSN: | 2329-0501 |
| Publisher: | Cell Press |
| Volume: | 24 |
| 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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