A novel hormone based anti-SSTR anti-CD3 T-cell engager for the treatment of neuroendocrine tumours

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Introduction: Somatostatin receptor 2 (SSTR2) is overexpressed in well-differentiated NETs.

Aim(s): We designed a novel bispecific T-cell engager targeting SSTR2 via Somatostatin-14, linked with a scFV-based anti-CD3.

Materials and methods: 293T cells expressing SSTR2 and GFP or GFP only and patient derived tumouroids from pancreatic NET liver metastasis were used as targets. Tumour-infiltrating lymphocytes (TILs) isolated from the same tumour samples and CD3+ T cells from peripheral blood of healthy donors or NET patients were used as effectors. Flow cytometry and Image Stream flow cytometry were used to determine the interaction of the molecule with CD3 and SSTR2 and formation of immune synapses. The engager-induced T-cell activation and cytotoxicity were evaluated by ELISA and real-time quantitative live-cell imaging. The effect of the molecule alone or octreotide alone on tumouroids was quantified by bioluminescence.

Conference:

Presenting Author: Pelle E

Authors: Pelle E, Cives M, Chaoul N, d'Angelo G, Medina E,

Keywords: T-cell engager, immunotherapy, tumouroids,