Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion

Show full item record



Permalink

http://hdl.handle.net/10138/198894

Citation

Kaartinen , T , Luostarinen , A , Maliniemi , P , Keto , J , Arvas , M , Belt , H , Koponen , J , Loskog , A , Mustjoki , S , Porkka , K , Yla-Herttuala , S & Korhonen , M 2017 , ' Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion ' , Cytotherapy , vol. 19 , no. 6 , pp. 689-702 . https://doi.org/10.1016/j.jcyt.2017.03.067

Title: Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion
Author: Kaartinen, Tanja; Luostarinen, Annu; Maliniemi, Pilvi; Keto, Joni; Arvas, Mikko; Belt, Heini; Koponen, Jonna; Loskog, Angelica; Mustjoki, Satu; Porkka, Kimmo; Yla-Herttuala, Seppo; Korhonen, Matti
Contributor: University of Helsinki, Medicum
University of Helsinki, Clinicum
Date: 2017-06
Language: eng
Number of pages: 14
Belongs to series: Cytotherapy
ISSN: 1465-3249
URI: http://hdl.handle.net/10138/198894
Abstract: Background. Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype. Methods. Lymphocytes were transduced with third-generation lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20 days) on the phenotype of the T-cell products were analyzed. Results. High IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. T memory stem cells (T-SCM, CD95(+)CD45RO(-)CD45RA(+)CD27(+)) were present variably during T-cell expansion. However, their presence was not IL-2 dependent but was linked to expansion kinetics. CD19-CART cells generated in these conditions displayed in vitro antileukemic activity. In summary, production of CART cells without any cytokine supplementation yielded the highest proportion of early memory T cells, provided a 10 fold cell expansion and the cells were functionally potent. Discussion. The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost:effective T-cell manufacturing.
Subject: chimeric antigen receptor T cells
effector function
human
interleukin-2
T-cell expansion
T-cell memory
TUMOR-INFILTRATING LYMPHOCYTES
ADOPTIVE IMMUNOTHERAPY
TRANSFER THERAPY
IN-VIVO
B-CELL
TELOMERE LENGTH
STEM-CELLS
CD8(+)
MALIGNANCIES
PERSISTENCE
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S1465324917305212_main.pdf 1.328Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record