Depletion of high-content CD14⁺ cells from apheresis products is critical for successful transduction and expansion of CAR T cells during large-scale cGMP manufacturing.

ABSTRACT: With the US Food and Drug Administration (FDA) approval of four CD19- and one BCMA-targeted chimeric antigen receptor (CAR) therapy for B cell malignancies, CAR T cell therapy has finally reached the status of a medicinal product. The successful manufacturing of autologous CAR T cell products is a key requirement for this promising treatment modality. By analyzing the composition of 214 apheresis products from 210 subjects across eight disease indications, we found that high CD14⁺ cell content poses a challenge for manufacturing CAR T cells, especially in patients with non-Hodgkin's lymphoma and multiple myeloma caused by the non-specific phagocytosis of the magnetic beads used to activate CD3⁺ T cells. We demonstrated that monocyte depletion via rapid plastic surface

SUBMITTER: Wang X 

PROVIDER: S-EPMC8411225 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature