Optimization of lymphapheresis for manufacturing autologous CAR-T cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2021-07-17

AUTHORS

Ikumi Yamanaka, Takuji Yamauchi, Tomoko Henzan, Teppei Sakoda, Kyoko Miyamoto, Hiroyuki Mishima, Hiroaki Ono, Yuhki Koga, Yasuhiro Nakashima, Koji Kato, Toshihiro Miyamoto, Shinichi Mizuno, Yoshihiro Ogawa, Shouichi Ohga, Koichi Akashi, Takahiro Maeda, Yuya Kunisaki

ABSTRACT

Collection of CD3+ lymphocytes via lymphapheresis is essential for manufacturing autologous chimeric antigen receptor (CAR) T cells. Optimization of timing and procedures for lymphapheresis for each patient is critical because patients often have progressive diseases and receive medications that could reduce T cell counts. We conducted a retrospective study of clinical data from 28 patients who underwent lymphapheresis for CD19-directed CAR-T therapy with tisagenlecleucel to identify factors that could affect CD3+ lymphocyte yields. The numbers of CD3+ cells in peripheral blood were significantly correlated with CD3+ cell yields (correlation coefficient r = 0.84), which enabled us to estimate the volume of blood to process before apheresis. We also found that small cell ratio (SCR) at the apheresis site precisely reflected the proportion of lymphocytes, especially in patients without circulating blasts (coefficient of determination: r2 = 0.9). We were able to predict the CD3+ cell yield and prevent excessive apheresis by measuring pre-apheresis circulating CD3+ cell counts and monitoring SCR. Collectively, these results will help us to establish a strategy for optimization of lymphapheresis procedures for CAR-T cell production on a patient-by-patient basis. More... »

PAGES

449-458

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-021-03191-x

DOI

http://dx.doi.org/10.1007/s12185-021-03191-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1139745739

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34275066


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24 schema:description Collection of CD3+ lymphocytes via lymphapheresis is essential for manufacturing autologous chimeric antigen receptor (CAR) T cells. Optimization of timing and procedures for lymphapheresis for each patient is critical because patients often have progressive diseases and receive medications that could reduce T cell counts. We conducted a retrospective study of clinical data from 28 patients who underwent lymphapheresis for CD19-directed CAR-T therapy with tisagenlecleucel to identify factors that could affect CD3+ lymphocyte yields. The numbers of CD3+ cells in peripheral blood were significantly correlated with CD3+ cell yields (correlation coefficient r = 0.84), which enabled us to estimate the volume of blood to process before apheresis. We also found that small cell ratio (SCR) at the apheresis site precisely reflected the proportion of lymphocytes, especially in patients without circulating blasts (coefficient of determination: r2 = 0.9). We were able to predict the CD3+ cell yield and prevent excessive apheresis by measuring pre-apheresis circulating CD3+ cell counts and monitoring SCR. Collectively, these results will help us to establish a strategy for optimization of lymphapheresis procedures for CAR-T cell production on a patient-by-patient basis.
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31 schema:keywords CAR T cells
32 CAR T-cell production
33 CAR-T therapy
34 CD19
35 CD3
36 T cells
37 T-cell counts
38 antigen receptor T cells
39 apheresis
40 autologous CAR-T cells
41 autologous chimeric antigen receptor (CAR) T cells
42 basis
43 blasts
44 blood
45 cell count
46 cell production
47 cell ratio
48 cell yield
49 cells
50 chimeric antigen receptor T cells
51 clinical data
52 collection
53 count
54 data
55 disease
56 factors
57 lymphapheresis
58 lymphocyte yield
59 lymphocytes
60 medications
61 number
62 number of CD3
63 optimization
64 optimization of timing
65 patient basis
66 patients
67 peripheral blood
68 procedure
69 production
70 progressive disease
71 proportion
72 proportion of lymphocytes
73 ratio
74 receptor T cells
75 results
76 retrospective study
77 sites
78 strategies
79 study
80 therapy
81 timing
82 tisagenlecleucel
83 volume
84 volume of blood
85 yield
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