A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy
| Autor: | Massimo Di Nicola, Alessandro Satta, Mariangela Figini, Delia Mezzanzanica, Nadia Zaffaroni, Francesco Caroli, Barbara Frigerio, Alessandro Massimo Gianni, Giulia Grazia, Andrea Anichini, Francesco Raspagliesi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Male CD3 Complex medicine.medical_treatment T-Lymphocytes Immunology Lymphocyte Activation 03 medical and health sciences 0302 clinical medicine Antigen In vivo Antigens Neoplasm TRAIL-R2 Cell Line Tumor Neoplasms Antibodies Bispecific Immunology and Allergy Medicine Humans Cytotoxicity Original Research business.industry malignant ascites Immunotherapy medicine.disease T-cell retargeting In vitro bispecific antibody Receptors TNF-Related Apoptosis-Inducing Ligand 030104 developmental biology Cancer cell Cancer research Female lcsh:RC581-607 business Ovarian cancer Ex vivo 030215 immunology |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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