Oncolytic HSV-1 in combination with lenalidomide for plasma cell neoplasms

( 最大 2000 件 )
URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/29141
タイトル
Oncolytic HSV-1 in combination with lenalidomide for plasma cell neoplasms
ファイル
内容記述

Abstract

Oncolytic viruses exert an anti-tumour effect through two mechanisms: direct oncolytic and indirect immune-mediated mechanisms. Although oncolytic herpes simplex virus type 1 (HSV-1) has been approved for melanoma treatment and is being examined for its applicability to a broad spectrum of malignancies, it is not known whether it has an anti-myeloma effect. In the present study, we show that the third-generation oncolytic HSV-1, T-01, had a direct oncolytic effect on five of six human myeloma cell lines in vitro. The anti-tumour effect was enhanced in the presence of peripheral blood mononuclear cells (PBMCs) from healthy individuals and, to a lesser extent, from patients with myeloma. The enhancing effect of PBMCs was abrogated by blocking type I interferons (IFNs) or by depleting plasmacytoid dendritic cells (pDCs) or natural killer (NK) cells, suggesting that pDC-derived type I IFNs and NK cells dominated the anti-tumour effect. Furthermore, the combination of T-01 and lenalidomide exhibited enhanced cytotoxicity, and the triple combination of T-01, lenalidomide and IFN-α had a maximal effect. These data indicate that oncolytic HSV-1 represents a viable therapy for plasma cell neoplasms through direct oncolysis and immune activation governed by pDCs and NK cells. Lenalidomide is likely to augment the anti-myeloma effect of HSV-1.

Keywords:

HSV-1; immunotherapy; lenalidomide; myeloma; oncolytic virus

(医博甲758)

著者
著者 奥 真紀
著者(ヨミ) オク マキ
著者(別表記) Maki Oku
掲載誌
British journal of haematology
掲載誌(別表記)
Br J Haematol.
192
2
開始ページ
343
終了ページ
353
出版者
British Society for Haematology
Wiley
出版年月日
2020-11-20
ISSN
0007-1048
NCID
AA00574570
PMID
33216988
DOI
10.1111/bjh.17173
資料タイプ
学位論文
言語
英語
権利関係
Copyright © 2020 British Society for Haematology and John Wiley & Sons Ltd.
This is the Accepted Version of the following article: Oncolytic HSV-1 in combination with lenalidomide for plasma cell neoplasms; British journal of haematology; Volume 192 Number 2 (2020)) Pages: 343-353; doi: 10.1111/bjh.17173 , which has been published in final form at https://doi.org/10.1111/bjh.17173 .
該当なし
学位授与番号
博甲第758号
学位授与年月日
2020-12-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
Copyright (C) 2009 Kagawa University All rights reserved.