Title: Construction of a recombinant non-mitogenic anti-human CD3 antibody
Authors: Hinojosa, Luis E
Hernández, Tays
de Acosta, Cristina Mateo
Montero, Enrique
Pérez, Rolando
L√≥pez-Requena, Alejandro # ×
Issue Date: Apr-2010
Series Title: Hybridoma (2005) vol:29 issue:2 pages:115-24
Article number: 10.1089/hyb.2009.0042
Abstract: IOR-T3, a mouse monoclonal antibody specific for human CD3, has been successfully used in the treatment of acute transplant rejection due to its potential as T-cell immunosuppressant. In the present work we report the construction of a human IgG1 chimeric variant of IOR-T3, named T3q. In order to reduce the T-cell activating capacity of the newly obtained chimeric molecule, the two leucine residues at positions 234 and 235 of the CH2 region were replaced by alanines, obtaining the T3q(Ala/Ala) molecule. In vitro evaluation of T3q and T3q(Ala/Ala) showed that there were no differences in the recognition of human CD3 in comparison with murine IOR-T3. However, the Fc-mutated version T3q(Ala/Ala) displayed a much weaker FcgammaR binding capacity than the unmutated chimeric molecule T3q, as well as a reduced ability to induce T-cell proliferation, proinflammatory cytokine release (TNFalpha and IL-6), and early activation surface marker expression (CD25 and CD69). We also found that, unlike treatment with T3q, the reduction in T-cell proliferation was less marked on CD8(+) cells compared to the CD4(+) cells after treatment with T3q(Ala/Ala). These properties make T3q(Ala/Ala) an attractive clinical alternative as an immunoregulatory agent endowed with reduced toxicity.
ISSN: 1554-0014
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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