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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02514

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

 Alessandro Satta1,  Giulia Grazia2, Francesco Caroli3,  Barbara Frigerio1,  Massimo Di Nicola4, Francesco Raspagliesi5,  Delia Mezzanzanica2, Nadia Zaffaroni1,  Alessandro M. Gianni4, Andrea Anichini2* and  Mariangela Figini1*
  • 1Department of Applied Research and Technical Development, National Tumor Institute (Italy), Italy
  • 2Department of Research, National Tumor Institute (Italy), Italy
  • 3Laboratory medicine departement, Ospedale Niguarda Ca' Granda, Italy
  • 4Department of Medical Oncology and Hematology, National Tumor Institute (Italy), Italy
  • 5Surgery Department, National Tumor Institute (Italy), Italy

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 towards 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.

Keywords: bispecific antibody, TRAIL-R2/DR5, TRAIL-receptor 2/ Death – receptor 5, Immunotherapy, T cell retargeting, malignant ascites

Received: 30 May 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Satta, Grazia, Caroli, Frigerio, Di Nicola, Raspagliesi, Mezzanzanica, Zaffaroni, Gianni, Anichini and Figini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
PhD. Andrea Anichini, National Tumor Institute (Italy), Department of Research, Milan, Lombardy, Italy, andrea.anichini@istitutotumori.mi.it
PhD. Mariangela Figini, National Tumor Institute (Italy), Department of Applied Research and Technical Development, Milan, Italy, mariangela.figini@istitutotumori.mi.it