PMID: 8968099Dec 1, 1996Paper

CD3-CD28 costimulation as a means to avoiding T cell preactivation in bispecific monoclonal antibody-based treatment of ovarian carcinoma

Cancer Research
A MazzoniS Canevari

Abstract

One of the major limitations to the immunotherapy of ovarian carcinoma based on the use of anti-CD3/antitumor bispecific monoclonal antibodies (bi-mAb) is the need for preactivation of effector cells ex vivo, because cross-linking of the T cell receptor-CD3 complex per se may lead to T-cell unresponsiveness or even apoptosis. The bi-mAb OC/TR, which recognizes the folate-binding protein (FBP) overexpressed in 90% of ovarian carcinomas and the CD3 molecule on T cells, has demonstrated efficacy in a clinical setting. Here we investigated the possibility of delivering accessory signals to OC/TR-retargeted peripheral blood mononuclear cells (PBMCs) via an anti-CD28 mAb or an anti-FBP/anti-CD28 bi-mAb. Coculture of resting PBMCs from healthy donors with OC/TR, anti-FBP/anti-CD28 bi-mAb, and FBP+ tumor cell lines resulted in a highly activated phenotype of effector cells and in a dramatic in vitro growth inhibition of the target cells without an increase in OC/TR-redirected lysis. Whereas both the CD4 and CD8 T cell subsets were involved in the growth inhibition, only the CD8 subpopulation accounted for the cytotoxic activity. The in vitro tumor growth inhibition was mediated mainly by soluble factors, which were active on both FBP+ ...Continue Reading

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