Development of Anti-SSTR CAR T Cells for Future Treatment of NETs

#3004

Introduction: NETs overexpress somatostatin receptors (SSTRs).

Aim(s): To investigate the antitumor activity of chimeric antigen receptor (CAR) T cells directed against SSTRs.

Materials and methods: A second-generation CAR-like construct containing two molecules of octreotide in the extracellular moiety and CD28 as costimulatory module was cloned in a pMSGV1-28Z retroviral vector and then transduced in CD8+ T cells. Luciferase+ (Luc+) BON1, CM and QGP1 NET cells were screened for membrane SSTR2/5 expression by WB and flow cytometry. Co-culture experiments were performed at different effector:target (E:T) ratios for up to 48 hrs. Tumor cell cytotoxicity was assessed by bioluminescence imaging. The release of IFN-γ, IL-2 and TNF-α by activated CAR T cells was investigated by ELISA. NSG female mice (n=6/group) were subcutaneously injected with 4x106 Luc+ NET cells, and were then intravenously treated with 1x106 anti-SSTR CAR T cells, or untransduced (UT) T cells. Excised tumors were subjected to PCR to assess the infiltration of CAR T cells.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Cives M

Authors: Mandriani B, Cives M, Pelle' E, Quaresmini D, Ramello M,

Keywords: CAR T cells, adoptive cellular immunotherapy, NETs,