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Antibody-directed s...
Antibody-directed superantigen-mediated T-cell killing of myeloid leukaemic cell line cells
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- Gidlöf, Cecilia (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,KITM
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Carlson, Barbro (author)
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Dohlsten, Mikael (author)
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- Tötterman, Thomas H. (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,KITM
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(creator_code:org_t)
- 2009-04-24
- 1998
- English.
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 60:4, s. 233-239
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Keyword
- myeloid leukaemic cell line cells
- CD13
- CD33
- superantigen
- monoclonal antibody
- cytotoxic T cells
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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