A Bispecific Antibody to Link a TRAIL-Based Antitumor Approach to Immunotherapy.
Front Immunol
; 10: 2514, 2019.
Article
em En
| MEDLINE
| ID: mdl-31708930
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo CD3
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Anticorpos Biespecíficos
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Receptores do Ligante Indutor de Apoptose Relacionado a TNF
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Antígenos de Neoplasias
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article