CD18 Antibody Application Blocks Unwanted Off-Target T Cell Activation Caused by Bispecific Antibodies.
CD18
T cell activation
bispecific antibodies
cytokine release syndrome
immunotherapy
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
13 Sep 2021
13 Sep 2021
Historique:
received:
22
07
2021
revised:
03
09
2021
accepted:
10
09
2021
entrez:
28
9
2021
pubmed:
29
9
2021
medline:
29
9
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34572822
pii: cancers13184596
doi: 10.3390/cancers13184596
pmc: PMC8467378
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Deutsche Krebshilfe
ID : 111828
Organisme : Germany's Excellence Strategy
ID : EXC 2180/1
Organisme : Deutsche Krebshilfe
ID : 70112914
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Deutschen Konsortium für Translationale Krebsforschung
ID : n/a
Organisme : Deutsche Forschungsgemeinschaft
ID : SA1360/7-3
Organisme : Deutsche Forschungsgemeinschaft
ID : SA1360/9-1
Organisme : Wilhelm Sander-Stiftung
ID : 2007.115.3
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