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Combining CAR T cel...
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Karlsson, S. C. HannahUppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
(författare)
Combining CAR T cells and the Bcl-2 family apoptosis inhibitor ABT-737 for treating B-cell malignancy
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2013-06-21
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Springer Science and Business Media LLC,2013
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-204980
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-204980URI
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https://doi.org/10.1038/cgt.2013.35DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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B-cell malignancies upregulate the B-cell lymphoma 2 (Bcl-2) family inhibitors of the intrinsic apoptosis pathway, making them therapy resistant. However, small-molecule inhibitors of Bcl-2 family members such as ABT-737 restore a functional apoptosis pathway in cancer cells, and its oral analog ABT-263 (Navitoclax) has entered clinical trials. Gene engineered chimeric antigen receptor (CAR) T cells also show promise in B-cell malignancy, and as they induce apoptosis via the extrinsic pathway, we hypothesized that small-molecule inhibitors of the Bcl-2 family may potentiate the efficacy of CAR T cells by engaging both apoptosis pathways. CAR T cells targeting CD19 were generated from healthy donors as well as from pre-B-ALL (precursor-B acute lymphoblastic leukemia) patients and tested together with ABT-737 to evaluate apoptosis induction in five B-cell tumor cell lines. The CAR T cells were effective even if the cell lines exhibited different apoptosis resistance profiles, as shown by analyzing the expression of apoptosis inhibitors by PCR and western blot. When combining T-cell and ABT-737 therapy simultaneously, or with ABT-737 as a presensitizer, tumor cell apoptosis was significantly increased. In conclusion, the apoptosis inducer ABT-737 enhanced the efficacy of CAR T cells and could be an interesting drug candidate to potentiate T-cell therapy.
Ämnesord och genrebeteckningar
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ABT-737
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BH3 mimetics
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engineered T cells
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CAR
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Bcl-2
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pre-B-ALL
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lindqvist, A. C.Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
(författare)
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Fransson, MoaUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)moafr634
(författare)
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Paul-Wetterberg, GabriellaUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)gabrpaul
(författare)
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Nilsson, BoUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)bonils
(författare)
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Essand, MagnusUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)magnessa
(författare)
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Nilsson, KristinaUppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)krisnil
(författare)
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Frisk, PerUppsala universitet,Pediatrik(Swepub:uu)pefri226
(författare)
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Jernberg-Wiklund, HelenaUppsala universitet,Hematologi och immunologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)helenajw
(författare)
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Loskog, S. I. A.Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
(författare)
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Uppsala universitetScience for Life Laboratory, SciLifeLab
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cancer Gene Therapy: Springer Science and Business Media LLC20:7, s. 386-3930929-19031476-5500
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