Destruction of Nonimmunogenic Mammary Tumor Cells by a Fusogenic Oncolytic Herpes Simplex Virus Induces Potent Antitumor Immunity

In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic onc...

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Veröffentlicht in:Molecular therapy 2004-05, Vol.9 (5), p.658-665
Hauptverfasser: Nakamori, Mikihito, Fu, Xinping, Rousseau, Raphael, Chen, Si-Yi, Zhang, Xiaoliu
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container_issue 5
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container_title Molecular therapy
container_volume 9
creator Nakamori, Mikihito
Fu, Xinping
Rousseau, Raphael
Chen, Si-Yi
Zhang, Xiaoliu
description In principle, destruction of tumor cells in vivo by oncolytic agents would release the entire repertoire of tumor antigens in their natural forms, leading to effective antitumor immunity. This goal has been elusive despite extensive testing of numerous strategies. We developed a doubly fusogenic oncolytic herpes simplex virus (Synco-2D) that kills tumor cells by a unique dual mechanism combining direct cytolysis with syncytial formation induced by cell membrane fusion. A single intratumor injection of Synco-2D induced strong antitumor immunity against an otherwise nonimmunogenic murine mammary tumor growing in immune-competent mice. CD8+ T cells were the primary mediators of immunity, contributing to the destruction of both primary and metastatic tumors. We conclude that the fusogenic capacity of Synco-2D enables it to elicit antitumor immunity exceeding that induced by more conventional oncolytic viruses.
doi_str_mv 10.1016/j.ymthe.2004.02.019
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subjects Animals
Antigens
Carcinoma - immunology
Carcinoma - virology
Cell Line
Cell Survival
Cytotoxicity
Drug dosages
Female
Gene therapy
Herpes viruses
Immunotherapy
Infections
Interferon-gamma - immunology
Interleukin-10 - immunology
Lung Neoplasms - pathology
Lung Neoplasms - secondary
Lymphocyte Depletion
Mammary Neoplasms, Experimental - immunology
Mammary Neoplasms, Experimental - virology
Medical schools
Medicine
Membrane Fusion
Metastasis
Mice
Mice, Inbred BALB C
Neoplasm Metastasis - pathology
Neoplasm Transplantation
Simplexvirus - physiology
T-Lymphocytes, Cytotoxic - immunology
Tumor Escape - immunology
Tumors
Vaccines
title Destruction of Nonimmunogenic Mammary Tumor Cells by a Fusogenic Oncolytic Herpes Simplex Virus Induces Potent Antitumor Immunity
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