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Low interleukin-2 c...
Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion
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- Kaartinen, Tanja (författare)
- Finnish Red Cross Blood Serv, Adv Cell Therapy Ctr, Kivihaantie 7, Helsinki 00310, Finland.
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- Luostarinen, Annu (författare)
- Finnish Red Cross Blood Serv, Adv Cell Therapy Ctr, Kivihaantie 7, Helsinki 00310, Finland.
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- Maliniemi, Pilvi (författare)
- Finnish Red Cross Blood Serv, Adv Cell Therapy Ctr, Kivihaantie 7, Helsinki 00310, Finland.;Finnish Red Cross Blood Serv, Res & Dev, Helsinki, Finland.
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- Keto, Joni (författare)
- Finnish Red Cross Blood Serv, Res & Dev, Helsinki, Finland.
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- Arvas, Mikko (författare)
- Finnish Red Cross Blood Serv, Res & Dev, Helsinki, Finland.
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- Belt, Heini (författare)
- Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Biotechnol & Mol Med, Kuopio, Finland.
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- Koponen, Jonna (författare)
- Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Biotechnol & Mol Med, Kuopio, Finland.
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- Loskog, Angelica S., 1973- (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Mustjoki, Satu (författare)
- Univ Helsinki, Biomedicum Helsinki, Dept Med, Hematol Res Unit Helsinki,Div Hematol, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem & Hematol, Helsinki, Finland.
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- Porkka, Kimmo (författare)
- Univ Helsinki, Biomedicum Helsinki, Dept Med, Hematol Res Unit Helsinki,Div Hematol, Helsinki, Finland.
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- Ylä-Herttuala, Seppo (författare)
- Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Biotechnol & Mol Med, Kuopio, Finland.;Kuopio Univ Hosp, Ctr Heart, Kuopio, Finland.
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- Korhonen, Matti (författare)
- Finnish Red Cross Blood Serv, Adv Cell Therapy Ctr, Kivihaantie 7, Helsinki 00310, Finland.
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Finnish Red Cross Blood Serv, Adv Cell Therapy Ctr, Kivihaantie 7, Helsinki 00310, Finland Finnish Red Cross Blood Serv, Adv Cell Therapy Ctr, Kivihaantie 7, Helsinki 00310, Finland.;Finnish Red Cross Blood Serv, Res & Dev, Helsinki, Finland. (creator_code:org_t)
- ELSEVIER SCI LTD, 2017
- 2017
- Engelska.
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Ingår i: Cytotherapy. - : ELSEVIER SCI LTD. - 1465-3249 .- 1477-2566. ; 19:6, s. 689-702
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://www.cellthera...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- chimeric antigen receptor T cells
- effector function
- human
- interleukin-2
- T-cell expansion
- T-cell memory
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- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Kaartinen, Tanja
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Luostarinen, Ann ...
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Maliniemi, Pilvi
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Keto, Joni
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Arvas, Mikko
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Belt, Heini
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visa fler...
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Koponen, Jonna
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Loskog, Angelica ...
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Mustjoki, Satu
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Porkka, Kimmo
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Ylä-Herttuala, S ...
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Korhonen, Matti
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- Artiklar i publikationen
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Cytotherapy
- Av lärosätet
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Uppsala universitet