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Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing

Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing
Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing
Antibodies against human leukocyte antigen (HLA) class II, such as 1D10 or Lym-1, are currently being evaluated for the treatment of B-cell lymphomas. Previous studies have demonstrated that, in addition to IgG Fc receptors, the human myeloid IgA receptor (Fcalpha RI, CD89) also effectively triggered tumor cell killing. Therefore, we used the variable light and heavy chain sequences from another murine anti-HLA class II hybridoma, F3.3, to generate a panel of chimeric human/mouse antibodies, including human immunoglobulin A1 (IgA1), IgA2, IgG1, IgG2, IgG3, and IgG4. Antibody production was accomplished by stable transfection of baby hamster kidney cells, and binding activity and specificity were confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. All constructs demonstrated similar binding to HLA class II. Functional studies revealed that chimeric IgG1, IgA1, and IgA2 triggered similar levels of tumor cell lysis. Analyses of effector populations, however, demonstrated that killing by chimeric IgG1 constructs was triggered mainly by human mononuclear cells and complement, while IgA1 and IgA2 mediated effective lysis by polymorphonuclear neutrophils. Importantly, IgG1 and both IgA isotypes were equally effective at killing freshly isolated human chronic lymphocytic leukemia cells. Chimeric IgA antibodies against HLA class II may constitute attractive reagents for lymphoma therapy.
0006-4971
4574-4580
Dechant, Michael
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Vidarsson, Gestur
60d2b2a0-f33c-4b40-8f9e-2557ddd4a50e
Stockmeyer, Bernhard
dac08105-8b0d-4bb2-b486-1ae1f6df9557
Repp, Roland
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Glennie, Martin J.
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Gramatzki, Martin
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van de Winkel, G.J
70d2bbca-c064-482c-98e2-4ae2b0895912
Valerius, Thomas
f3f84699-e0a5-4f3d-9d4e-405c0b3bc571
Dechant, Michael
0ce79062-f196-404c-91d3-5289c1de2533
Vidarsson, Gestur
60d2b2a0-f33c-4b40-8f9e-2557ddd4a50e
Stockmeyer, Bernhard
dac08105-8b0d-4bb2-b486-1ae1f6df9557
Repp, Roland
762b8881-3417-4c23-89c8-c2c44032b2bb
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Gramatzki, Martin
2e69f942-5997-4920-8b88-30d7ffe4c6b9
van de Winkel, G.J
70d2bbca-c064-482c-98e2-4ae2b0895912
Valerius, Thomas
f3f84699-e0a5-4f3d-9d4e-405c0b3bc571

Dechant, Michael, Vidarsson, Gestur, Stockmeyer, Bernhard, Repp, Roland, Glennie, Martin J., Gramatzki, Martin, van de Winkel, G.J and Valerius, Thomas (2002) Chimeric IgA antibodies against HLA class II effectively trigger lymphoma cell killing. Blood, 100 (13), 4574-4580. (doi:10.1182/blood-2002-03-0687).

Record type: Article

Abstract

Antibodies against human leukocyte antigen (HLA) class II, such as 1D10 or Lym-1, are currently being evaluated for the treatment of B-cell lymphomas. Previous studies have demonstrated that, in addition to IgG Fc receptors, the human myeloid IgA receptor (Fcalpha RI, CD89) also effectively triggered tumor cell killing. Therefore, we used the variable light and heavy chain sequences from another murine anti-HLA class II hybridoma, F3.3, to generate a panel of chimeric human/mouse antibodies, including human immunoglobulin A1 (IgA1), IgA2, IgG1, IgG2, IgG3, and IgG4. Antibody production was accomplished by stable transfection of baby hamster kidney cells, and binding activity and specificity were confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. All constructs demonstrated similar binding to HLA class II. Functional studies revealed that chimeric IgG1, IgA1, and IgA2 triggered similar levels of tumor cell lysis. Analyses of effector populations, however, demonstrated that killing by chimeric IgG1 constructs was triggered mainly by human mononuclear cells and complement, while IgA1 and IgA2 mediated effective lysis by polymorphonuclear neutrophils. Importantly, IgG1 and both IgA isotypes were equally effective at killing freshly isolated human chronic lymphocytic leukemia cells. Chimeric IgA antibodies against HLA class II may constitute attractive reagents for lymphoma therapy.

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Published date: 2002

Identifiers

Local EPrints ID: 26276
URI: http://eprints.soton.ac.uk/id/eprint/26276
ISSN: 0006-4971
PURE UUID: 0133206b-48bd-4a9d-832f-5fdb4afee063

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Date deposited: 20 Apr 2006
Last modified: 15 Jul 2019 19:14

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Contributors

Author: Michael Dechant
Author: Gestur Vidarsson
Author: Bernhard Stockmeyer
Author: Roland Repp
Author: Martin Gramatzki
Author: G.J van de Winkel
Author: Thomas Valerius

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