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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Satta A,Grazia G,Caroli F,Frigerio B,Di Nicola M,Raspagliesi F,Mezzanzanica D,Zaffaroni N,Gianni AM,Anichini A,Figini Mdoi
10.3389/fimmu.2019.02514subject
Has Abstractpub_date
2019-10-25 00:00:00pages
2514issn
1664-3224journal_volume
10pub_type
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