Cross-linking tumor cells with effector cells via CD55 with a bispecific mAb induces beta-glucan-dependent CR3-dependent cellular cytotoxicity

European Journal of Immunology
Kyra A GeldermanArko Gorter

Abstract

Complement (C) regulatory proteins decrease the effectiveness of immunotherapeutic anti-cancer antibodies. Bispecific mAb (bi-mAb) that target a tumor antigen and simultaneously inhibit a C regulator increase the effectiveness of such a therapy. Here we investigated the mechanism by which bi-mAb increase tumor cell lysis. Apart from C-dependent cytotoxicity, C activation can lead to complement receptor 3 (CR3)-dependent cellular cytotoxicity (CR3-DCC) by CR3-positive effector cells in the presence of beta-glucan. Here we show that an anti-Ep-CAM*anti-CD55 bi-mAb induced more than threefold higher CR3-DCC (71%) of human colorectal cancer cells compared with anti-Ep-CAM alone (20%). This CR3-DCC was dependent on the binding of the anti-CD55 arm of tumor-bound anti-Ep-CAM*anti-CD55 bi-mAb to effector cell CD55, CR3 priming by beta-glucan and the presence of iC3b on the target cell. Comparable lysis could be obtained in the absence of iC3b, when CR3 and CD55 were cross-linked on the effector cells, suggesting cooperation between CD55 and CR3 in signal transduction. Tumor cells with low antigen expression were effectively lysed via this mechanism in contrast to direct C-dependent cytotoxicity. These data imply that the effectiveness...Continue Reading

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Citations

Oct 1, 2011·Archivum Immunologiae Et Therapiae Experimentalis·Martin KolevRossen Donev
May 8, 2018·Scandinavian Journal of Immunology·H Bareke, J Akbuga
Jun 17, 2020·Expert Review of Clinical Immunology·Maryam Balibegloo, Nima Rezaei
Jul 11, 2012·European Journal of Immunology·Carmelo BiondoConcetta Beninati
Oct 30, 2020·Antibodies·Margot RevelLubka T Roumenina

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