Potent soluble linear T cell engagers for the ex vivo expansion of human T cells

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B950
Abstract ID: 5840

Presenting Author:
Jean Gariepy , Senior Scientist at Sunnybrook Res. Inst., Univ. of Toronto

Abstract:

Adoptive cell therapy, is a treatment modality where immune cells are used or engineered to eliminate cancer or to treat inflammatory diseases. One example is the infusion of tumor-reactive T cells into patients with cancer to provide antitumor immunity. The ex vivo expansion and differentiation of such T cells are key parameters that affect their therapeutic potential. Human T cells are presently expanded in culture through the use of immobilized anti-CD3 and anti-CD28 mAbs, or expressed on cells, or assembled as antibody complexes. Here we report instead the design of two small, soluble bispecific single-chain variable fragment constructs agonizing both CD3 and CD28 pathways.  These minimal, soluble T cell engagers are produced in high yield in HEK293 eukaryotic cells and induce the proliferation of both human CD4+ and CD8+ human T cells ex vivo when used at concentrations in the femtomolar range.Importantly, they favor the ex vivo preferential expansion of less differentiated human CD8+ CD27+ human T cells over the course of 12 days, a T cell subset that is potentially more suited for adoptive cell therapy. We have recently observed that the performance of these simple T cell engagers compares well with existing anti-CD3/anti-CD28 mAb-based reagents such as TransAct in terms of expanding functional CD19-targeted CAR-T cells. The differentiation profile induced by these simple T cell engagers and their potency may favor their use in expanding human T cell subsets ex vivo.