Abstract

T-cell-based immunotherapy strategies have profoundly improved the clinical management of several solid tumors and hematological malignancies. A recently developed and promising immunotherapy approach is to redirect polyclonal MHC-unrestricted T lymphocytes toward cancer cells by bispecific antibodies (bsAbs) that engage the CD3 complex and a tumor-associated antigen (TAA). The TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) is an attractive immunotherapy target, frequently expressed by neoplastic cells, that we decided to exploit as a TAA. We found that a TRAIL-R2xCD3 bsAb efficiently activates T cells and specifically redirect their cytotoxicity against cancer cells of different origins in vitro, thereby demonstrating its potential as a pan-carcinoma reagent. Moreover, to mimic in vivo conditions, we assessed its ability to retarget T-cell activity in an ex vivo model of ovarian cancer patients’ ascitic fluids containing both effector and target cells—albeit with a suboptimal effector-to-target ratio—with remarkable results.

Original languageEnglish
Article number2514
JournalFrontiers in Immunology
Volume10
Issue numberOCT
DOIs
Publication statusPublished - Jan 1 2019

Keywords

  • Bispecific antibody
  • Immunotherapy
  • Malignant ascites
  • T-cell retargeting
  • TRAIL-R2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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