Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia.
Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia.
复制标题
作者：
The naturally occurring oncolytic virus (OV), reovirus, replicates in cancer cells causing direct cytotoxicity, and can activate innate and adaptive immune responses to facilitate tumour clearance. Reovirus is safe, well tolerated and currently in clinical testing for the treatment of multiple myeloma, in combination with dexamethasone/carfilzomib. Activation of natural killer (NK) cells has been observed after systemic delivery of reovirus to cancer patients; however, the ability of OV to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is unexplored. This study elucidates the potential of oncolytic reovirus for the treatment of chronic lymphocytic leukaemia (CLL), both as a direct cytotoxic agent and as an immunomodulator. We demonstrate that reovirus: (i) is directly cytotoxic against CLL, which requires replication-competent virus; (ii) phenotypically and functionally activates patient NK cells via a monocyte-derived interferon-α (IFNα)-dependent mechanism; and (iii) enhances ADCC-mediated killing of CLL in combination with anti-CD20 antibodies. Our data provide strong preclinical evidence to support the use of reovirus in combination with anti-CD20 immunotherapy for the treatment of CLL.
登录
查看更多内容
影响因子：
3.6
作者：
Glennie, Martin J.;French, Ruth R.;Taylor, Ronald P.
通讯作者：
Taylor, Ronald P.
影响因子：
4.4
作者：
Errington, Fiona;Steele, Lynette;Melcher, Alan
通讯作者：
Melcher, Alan
影响因子：
5.1
作者：
Errington, F.;White, C. L.;Melcher, A. A.
通讯作者：
Melcher, A. A.
DOI：
10.1158/1078-0432.ccr-10-0054
发表时间：
2010-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Harrington KJ;Karapanagiotou EM;Roulstone V;Twigger KR;White CL;Vidal L;Beirne D;Prestwich R;Newbold K;Ahmed M;Thway K;Nutting CM;Coffey M;Harris D;Vile RG;Pandha HS;Debono JS;Melcher AA
通讯作者：
Melcher AA
影响因子：
4.6
作者：
El-Sherbiny, Y. M.;Holmes, T. D.;Cook, G. P.
通讯作者：
Cook, G. P.