A novel hormone-based anti-SSTR T-cell engager for the treatment of neuroendocrine tumors

#3758

Introduction: Somatostatin receptors (SSTRs) are overexpressed by well-differentiated neuroendocrine tumors (NETs).

Aim(s): We designed a novel bispecific T-cell engager (BiTE®)-like molecule composed of 2 molecules of Somatostatin, the hormone that physiologically binds the SSTRs, linked with a scFV-based anti-CD3.

Materials and methods: The recombinant protein was expressed using insect cells. CD3+ T cells from healthy donors and 293T cells transduced to concurrently express SSTR2 and GFP were cocultured, at different ratios E:T, in presence or absence of the molecule. SSTR2- parental 293T cell line was used as negative control. The binding potential towards the CD3 was determined by flow cytometry. Confocal microscopy was used to visualize interaction with SSTR2+ 293T cells. The molecule-induced T cell activation was evaluated measuring the IFNγ and Granzyme-B by ELISA and the CD25, CD69 and CD107 by flow cytometry. The molecule-induced cytotoxicity was assessed by real-time quantitative live-cell imaging.

Conference:

Presenting Author: Pelle E

Authors: Pelle E, Cives M, Medina E, Mason C, Snedal S,

Keywords: Bispecific T cell Engagers, CD3, SSTR, TILs, Immunotherapy,