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Addition of the CD2...
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Loskog, AngelicaUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
(författare)
Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells
- Artikel/kapitelEngelska2006
Förlag, utgivningsår, omfång ...
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2006-08-17
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Springer Science and Business Media LLC,2006
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-25752
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-25752URI
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https://doi.org/10.1038/sj.leu.2404366DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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T cells can be engineered to target tumor cells by transduction of tumor-specific chimeric receptors, consisting of an extracellular antigen-binding domain and an intracellular signaling domain. However, the peripheral blood of cancer patients frequently contains an increased number of T regulatory cells, which appear to inhibit immune reactivity. We have investigated the effects of T regulatory cells on chimeric T cells specific for the B-cell antigen CD19, as B-cell malignancies are attractive targets for chimeric T-cell therapy. When a CD19 single-chain Fv antibody was coupled to the CD3 zeta ( zeta) chain, there was sharply reduced activity on exposure to T regulatory cells, measured by CD19+ target-induced proliferation and cytotoxicity. By contrast, expression in T cells of a chimeric receptor consisting of the intracellular portion of the CD28 molecule fused to the zeta-chain and CD19 single-chain Fv not only produced a higher proliferative response and an increased nuclear factor kappa B activation but also sustained these activities in the presence of T regulatory cells. These effects are seen whether the chimeric T cells are derived from normal donors or from patients with B-cell chronic lymphocytic leukemia, indicating the potential for clinical application in B cell malignancies.
Ämnesord och genrebeteckningar
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chimeric T cells
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CD28
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T regulatory cells
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CD19
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B-CLL
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Giandomenico, ValeriaUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi(Swepub:uu)valegian
(författare)
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Rossig, C.
(författare)
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Pule, M.
(författare)
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Dotti, G.
(författare)
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Brenner, M. K.
(författare)
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Uppsala universitetInstitutionen för onkologi, radiologi och klinisk immunologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Leukemia: Springer Science and Business Media LLC20:10, s. 1819-18280887-69241476-5551
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Leukemia
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