Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia.

Autor:	Parrish C; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Scott GB; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Migneco G; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Scott KJ; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Steele LP; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Ilett E; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., West EJ; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Hall K; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Selby PJ; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Buchanan D; St James's University Hospital, Leeds, UK., Varghese A; St James's University Hospital, Leeds, UK., Cragg MS; Antibody and Vaccine Group, Cancer Sciences Unit, Southampton University, General Hospital, Southampton, UK., Coffey M; Oncolytics Biotech Inc., Calgary, AB, Canada., Hillmen P; Experimental Haematology, LICAP, University of Leeds, Leeds, UK., Melcher AA; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK., Errington-Mais F; Section of Oncology and Clinical Research, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, St James's University Hospital, Leeds, UK.
Jazyk:	angličtina
Zdroj:	Leukemia [Leukemia] 2015 Sep; Vol. 29 (9), pp. 1799-810. Date of Electronic Publication: 2015 Mar 27.
DOI:	10.1038/leu.2015.88
Abstrakt:	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.
Databáze:	MEDLINE
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