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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number2514
JournalFrontiers in Immunology
Volume10
Issue numberOCT
DOIs
Publication statusPublished - Jan 1 2019

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Bispecific Antibodies
Immunotherapy
T-Lymphocytes
Neoplasm Antigens
TNF-Related Apoptosis-Inducing Ligand Receptors
CD3 Antigens
Neoplasms
Ascitic Fluid
Hematologic Neoplasms
Ovarian Neoplasms
Carcinoma

Keywords

  • Bispecific antibody
  • Immunotherapy
  • Malignant ascites
  • T-cell retargeting
  • TRAIL-R2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "A bispecific antibody to link a trail-based antitumor approach to immunotherapy",
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.",
keywords = "Bispecific antibody, Immunotherapy, Malignant ascites, T-cell retargeting, TRAIL-R2",
author = "Alessandro Satta and Giulia Grazia and Francesco Caroli and Barbara Frigerio and {Di Nicola}, Massimo and Francesco Raspagliesi and Delia Mezzanzanica and Nadia Zaffaroni and Gianni, {Alessandro Massimo} and Andrea Anichini and Mariangela Figini",
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AU - Satta, Alessandro

AU - Grazia, Giulia

AU - Caroli, Francesco

AU - Frigerio, Barbara

AU - Di Nicola, Massimo

AU - Raspagliesi, Francesco

AU - Mezzanzanica, Delia

AU - Zaffaroni, Nadia

AU - Gianni, Alessandro Massimo

AU - Anichini, Andrea

AU - Figini, Mariangela

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Bispecific antibody

KW - Immunotherapy

KW - Malignant ascites

KW - T-cell retargeting

KW - TRAIL-R2

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