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CD18 antibody application blocks unwanted off-target T cell activation caused by bispecific antibodies

T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecifi...

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Main Authors: Kauer, Joseph (Author) , Vogt, Fabian (Author) , Hagelstein, Ilona (Author) , Hörner, Sebastian (Author) , Märklin, Melanie (Author) , Maurer, Stefanie (Author) , Salih, Helmut R. (Author) , Jung, Gundram (Author) , Zekri, Latifa (Author)
Format: Article (Journal)
Language:English
Published: 13 September 2021
In: Cancers
Year: 2021, Volume: 13, Issue: 18, Pages: 1-14
ISSN:2072-6694
DOI:10.3390/cancers13184596
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers13184596
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/13/18/4596
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Author Notes:Joseph Kauer, Fabian Vogt, Ilona Hagelstein, Sebastian Hörner, Melanie Märklin, Stefanie Maurer, Helmut R. Salih, Gundram Jung and Latifa Zekri
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Summary:T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecific CD3 antibodies to T cells in the absence of target cells may contribute to excessive cytokine release. We report here, in an in vitro setting, that off-target T cell activation is induced by bsAbs with high CD3 binding affinity and increased by endothelial- or lymphoid cells that act as stimulating bystander cells. Blocking antibodies directed against the adhesion molecules CD18/CD54 or CD2/CD58 markedly reduced this type of off-target T cell activation. CD18 blockade—in contrast to CD2—did not affect the therapeutic activity of various bsAbs. Since CD18 antibodies have been shown to be safely applicable in patients, blockade of this integrin holds promise as a potential target for the prevention of unwanted off-target T cell activation and allows the application of truly effective bsAb doses.
Item Description:Gesehen am 02.12.2021
This article belongs to the special issue "Cancer immunotherapy and immune-related adverse events"
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers13184596

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