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Antibody-directed s...
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Gidlöf, CeciliaUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,KITM
(författare)
Antibody-directed superantigen-mediated T-cell killing of myeloid leukaemic cell line cells
- Artikel/kapitelEngelska1998
Förlag, utgivningsår, omfång ...
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2009-04-24
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Wiley,1998
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-57010
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-57010URI
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https://doi.org/10.1111/j.1600-0609.1998.tb01029.xDOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Bacterial superantigens (SAgs) bound to MHC class II molecules on target cells are efficient activators of cytotoxic T cells expressing certain T cell receptor (TCR) Vbeta regions We described earlier that the specificity of the SAg Staphylococcus enterotoxin A (SEA) can be changed by introducing a D227A point mutation in the major MHC class II binding site and by genetically fusing the SEA mutant (SEAm) to protein A (PA). This SEAm-PA fusion protein can then be used to direct cytotoxic T cells to tumour cells coated with monoclonal antibodies (mAbs). In this communication, we tested the PA-SEAm fusion protein together with mAbs against the myeloid cell surface antigens CD13, CD15 and CD33. A SEA-reactive T cell line was used as effector cells against 10 different myeloid leukaemic cell lines. Optimal lysis of antigen positive leukaemic cells was obtained at a PA-SEAm concentration of 1 ng/ml and effector : target cell ratios of 15 : 1. No correlation between target cell sensitivity and the level of surface antigen expression could be seen. The 6 acute myeloid leukaemia (AML) cell lines tested appeared to be more sensitive than the 4 chronic myeloid leukaemia (CML) cell lines. The sensitivity of the AML cell line HL-60 could be improved further by stimulation with TNFalpha. This was accompanied by increased surface ICAM-1 expression whereas specific target molecule expression (CD13, CD33) was unchanged. This suggests that sensitivity to lysis is related to the leukaemic subtype and ICAM-1 expression but not to the tumour antigen density. Our results show that it is possible to direct cytotoxic T cells to myeloid leukaemia cells by using SAgs linked to mAbs, and encourage the construction and testing of a recombinant direct SAg-mAb fusion protein as a candidate drug for therapy of myeloid leukaemias.
Ämnesord och genrebeteckningar
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myeloid leukaemic cell line cells
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CD13
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CD33
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superantigen
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monoclonal antibody
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cytotoxic T cells
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Carlson, Barbro
(författare)
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Dohlsten, Mikael
(författare)
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Tötterman, Thomas H.Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,KITM(Swepub:uu)thomtott
(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:European Journal of Haematology: Wiley60:4, s. 233-2390902-44411600-0609
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