AUTHOR=Satta Alessandro , Grazia Giulia , Caroli Francesco , Frigerio Barbara , Di Nicola Massimo , Raspagliesi Francesco , Mezzanzanica Delia , Zaffaroni Nadia , Gianni Alessandro Massimo , Anichini Andrea , Figini Mariangela TITLE=A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02514 DOI=10.3389/fimmu.2019.02514 ISSN=1664-3224 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.