A bispecific antibody to link a trail-based antitumor approach to immunotherapy

Alessandro Satta, Giulia Grazia, Francesco Caroli, Barbara Frigerio, Massimo Di Nicola, Francesco Raspagliesi, Delia Mezzanzanica, Nadia Zaffaroni, Alessandro Massimo Gianni, Andrea Anichini, Mariangela Figini

Research output: Contribution to journalArticlepeer-review

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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