Fcγ receptor-mediated cross-linking codefines the immunostimulatory activity of anti-human CD96 antibodies
Authors: Rogel, A., Ibrahim, F.M., Thirdborough, S.M., Renart-Depontieu, F., Birts, C.N., Buchan, S.L., Preville, X., King, E.V. and Al-Shamkhani, A.
Journal: JCI Insight
Volume: 7
Issue: 19
eISSN: 2379-3708
DOI: 10.1172/jci.insight.158444
Abstract:New strategies that augment T cell responses are required to broaden the therapeutic arsenal against cancer. CD96, TIGIT, and CD226 are receptors that bind to a communal ligand, CD155, and transduce either inhibitory or activating signals. The function of TIGIT and CD226 is established, whereas the role of CD96 remains ambiguous. Using a panel of engineered antibodies, we discovered that the T cell stimulatory activity of anti-CD96 antibodies requires antibody cross-linking and is potentiated by Fcγ receptors. Thus, soluble “Fc silent” anti-CD96 antibodies failed to stimulate human T cells, whereas the same antibodies were stimulatory after coating onto plastic surfaces. Remarkably, the activity of soluble anti-CD96 antibodies was reinstated by engineering the Fc domain to a human IgG1 isotype, and it was dependent on antibody trans-cross-linking by FcγRI. In contrast, neither human IgG2 nor variants with increased Fcγ receptor IIB binding possessed stimulatory activity. Anti-CD96 antibodies acted directly on T cells and augmented gene expression networks associated with T cell activation, leading to proliferation, cytokine secretion, and resistance to Treg suppression. Furthermore, CD96 expression correlated with survival in HPV+ head and neck squamous cell carcinoma, and its cross-linking activated tumor-infiltrating T cells, thus highlighting the potential of anti-CD96 antibodies in cancer immunotherapy.
https://eprints.bournemouth.ac.uk/37427/
Source: Scopus
Fcγ receptor-mediated cross-linking codefines the immunostimulatory activity of anti-human CD96 antibodies.
Authors: Rogel, A., Ibrahim, F.M., Thirdborough, S.M., Renart-Depontieu, F., Birts, C.N., Buchan, S.L., Preville, X., King, E.V. and Al-Shamkhani, A.
Journal: JCI Insight
Volume: 7
Issue: 19
eISSN: 2379-3708
DOI: 10.1172/jci.insight.158444
Abstract:New strategies that augment T cell responses are required to broaden the therapeutic arsenal against cancer. CD96, TIGIT, and CD226 are receptors that bind to a communal ligand, CD155, and transduce either inhibitory or activating signals. The function of TIGIT and CD226 is established, whereas the role of CD96 remains ambiguous. Using a panel of engineered antibodies, we discovered that the T cell stimulatory activity of anti-CD96 antibodies requires antibody cross-linking and is potentiated by Fcγ receptors. Thus, soluble "Fc silent" anti-CD96 antibodies failed to stimulate human T cells, whereas the same antibodies were stimulatory after coating onto plastic surfaces. Remarkably, the activity of soluble anti-CD96 antibodies was reinstated by engineering the Fc domain to a human IgG1 isotype, and it was dependent on antibody trans-cross-linking by FcγRI. In contrast, neither human IgG2 nor variants with increased Fcγ receptor IIB binding possessed stimulatory activity. Anti-CD96 antibodies acted directly on T cells and augmented gene expression networks associated with T cell activation, leading to proliferation, cytokine secretion, and resistance to Treg suppression. Furthermore, CD96 expression correlated with survival in HPV+ head and neck squamous cell carcinoma, and its cross-linking activated tumor-infiltrating T cells, thus highlighting the potential of anti-CD96 antibodies in cancer immunotherapy.
https://eprints.bournemouth.ac.uk/37427/
Source: PubMed
Fcγ receptor-mediated cross-linking codefines the immunostimulatory activity of anti-human CD96 antibodies.
Authors: Rogel, A., Ibrahim, F.M., Thirdborough, S.M., Renart-Depontieu, F., Birts, C.N., Buchan, S.L., Preville, X., King, E.V. and Al-Shamkhani, A.
Journal: JCI insight
Volume: 7
Issue: 19
Pages: e158444
eISSN: 2379-3708
ISSN: 2379-3708
DOI: 10.1172/jci.insight.158444
Abstract:New strategies that augment T cell responses are required to broaden the therapeutic arsenal against cancer. CD96, TIGIT, and CD226 are receptors that bind to a communal ligand, CD155, and transduce either inhibitory or activating signals. The function of TIGIT and CD226 is established, whereas the role of CD96 remains ambiguous. Using a panel of engineered antibodies, we discovered that the T cell stimulatory activity of anti-CD96 antibodies requires antibody cross-linking and is potentiated by Fcγ receptors. Thus, soluble "Fc silent" anti-CD96 antibodies failed to stimulate human T cells, whereas the same antibodies were stimulatory after coating onto plastic surfaces. Remarkably, the activity of soluble anti-CD96 antibodies was reinstated by engineering the Fc domain to a human IgG1 isotype, and it was dependent on antibody trans-cross-linking by FcγRI. In contrast, neither human IgG2 nor variants with increased Fcγ receptor IIB binding possessed stimulatory activity. Anti-CD96 antibodies acted directly on T cells and augmented gene expression networks associated with T cell activation, leading to proliferation, cytokine secretion, and resistance to Treg suppression. Furthermore, CD96 expression correlated with survival in HPV+ head and neck squamous cell carcinoma, and its cross-linking activated tumor-infiltrating T cells, thus highlighting the potential of anti-CD96 antibodies in cancer immunotherapy.
https://eprints.bournemouth.ac.uk/37427/
Source: Europe PubMed Central
Fc-γ receptor-mediated crosslinking co-defines the immunostimulatory activity of anti-human CD96 antibodies.
Authors: Rogel, A., Ibrahim, F.M., Thirdborough, S.M., Renart-Depontieu, F., Birts, C.N., Buchan, S.L., Preville, X., King, E.V. and Al-Shamkhani, A.
Journal: JCI Insight
Volume: 7
Issue: 19
ISSN: 2379-3708
Abstract:New strategies that augment T-cell responses are required to broaden the therapeutic arsenal against cancer. CD96, TIGIT and CD226 are receptors that bind to a communal ligand, CD155, and transduce either inhibitory or activating signals. Whereas the function of TIGIT and CD226 is established, the role of CD96 remains ambiguous. Using a panel of engineered antibodies, we discovered that the T-cell stimulatory activity of anti-CD96 antibodies requires antibody crosslinking and is potentiated by Fc-gamma receptors. Thus, soluble 'Fc silent' anti-CD96 antibodies failed to stimulate human T cells, whereas the same antibodies were stimulatory after coating onto plastic surfaces. Remarkably, the activity of soluble anti-CD96 antibodies was reinstated by engineering the Fc domain to a human IgG1 isotype and was dependent on antibody trans-crosslinking by Fc-γRI. In contrast, neither human IgG2 nor variants with increased Fc-γ receptor IIB binding possessed stimulatory activity. Anti-CD96 antibodies acted directly on T cells and augmented gene expression networks associated with T-cell activation, leading to proliferation, cytokine secretion and resistance to regulatory T-cell suppression. Furthermore, CD96 expression correlated with survival in HPV+ head and neck squamous cell carcinoma and its crosslinking activated tumor-infiltrating T cells, thus highlighting the potential of anti-CD96 antibodies in cancer immunotherapy. .
https://eprints.bournemouth.ac.uk/37427/
Source: BURO EPrints