Synapse - 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

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 Journal Article

Authors:	Wang, X.; Borquez-Ojeda, O.; Stefanski, J.; Du, F.; Qu, J.; Chaudhari, J.; Thummar, K.; Zhu, M.; Shen, L. B.; Hall, M.; Gautam, P.; Wang, Y.; Sénéchal, B.; Sikder, D.; Adusumilli, P. S.; Brentjens, R. J.; Curran, K.; Geyer, M. B.; Mailankhody, S.; O'Cearbhaill, R.; Park, J. H.; Sauter, C.; Slovin, S.; Smith, E. L.; Rivière, I.
Article Title:	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 adhesion significantly reduces the CD14(+) monocyte content in the apheresis products and simultaneously boosts the CD3(+) content. We established a 40% CD14(+) threshold for the stratification of apheresis products across nine clinical trials and demonstrated the effectiveness of this procedure by comparing manufacturing runs in two phase 1 clinical trials. Our study suggests that CD14(+) content should be monitored in apheresis products, and that the manufacturing of CAR T cells should incorporate a step that lessens the CD14(+) cell content in apheresis products containing more than 40% to maximize the production success.
Keywords:	antigen; monocytes
Journal Title:	Molecular Therapy - Methods & Clinical Development
Volume:	22
ISSN:	2329-0501
Publisher:	Nature Publishing Group
Date Published:	2021-09-10
Start Page:	377
End Page:	387
Language:	English
ACCESSION:	WOS:000695842600032
DOI:	10.1016/j.omtm.2021.06.014
PROVIDER:	wos
PMCID:	PMC8411225
PUBMED:	34514029
Notes:	Article -- MSK author Sham Mailankody's last name is misspelled on the original publication -- Source: Wos