Combination of vaccine-strain measles and mumps virus synergistically kills a wide range of human hematological cancer cells: Special focus on acute myeloid leukemia

Li Feng Zhang; Darren Qian Cheng Tan; Anand D Jeyasekharan; Wen Son Hsieh; Anh Son Ho; Koji Ichiyama; Min Ye; Brendan Pang; Kenji Ohba; Xin Liu; Sanjay de Mel; Bui Khac Cuong; Wee Joo Chng; Akihide Ryo; Youichi Suzuki; Khay Guan Yeoh; Nguyen Linh Toan; Naoki Yamamoto

doi:10.1016/j.canlet.2014.08.034

Combination of vaccine-strain measles and mumps virus synergistically kills a wide range of human hematological cancer cells: Special focus on acute myeloid leukemia

Cancer Lett. 2014 Nov 28;354(2):272-80. doi: 10.1016/j.canlet.2014.08.034. Epub 2014 Sep 1.

Authors

Li Feng Zhang¹, Darren Qian Cheng Tan¹, Anand D Jeyasekharan², Wen Son Hsieh³, Anh Son Ho⁴, Koji Ichiyama¹, Min Ye¹, Brendan Pang⁵, Kenji Ohba¹, Xin Liu⁶, Sanjay de Mel⁶, Bui Khac Cuong⁴, Wee Joo Chng⁷, Akihide Ryo⁸, Youichi Suzuki¹, Khay Guan Yeoh⁸, Nguyen Linh Toan⁴, Naoki Yamamoto⁹

Affiliations

¹ Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² Department of Medicine, National University Hospital, Singapore.
³ Department of Otolaryngology - Head and Neck Surgery, National University Health System, Singapore; Cancer Science Institute, National University of Singapore, Singapore.
⁴ Department of Pathophysiology, Vietnam Military Medical University, Vietnam.
⁵ Department of Pathology, National University Health System and National University of Singapore, Singapore.
⁶ Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore.
⁷ Cancer Science Institute, National University of Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁸ Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Japan.
⁹ Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: micny@nus.edu.sg.

PMID: 25193462
DOI: 10.1016/j.canlet.2014.08.034

Abstract

Through combining vaccine-derived measles and mumps viruses (MM), we efficiently targeted a wide range of hematopoietic cancer cell lines. MM synergistically killed many cell lines including acute myeloid leukemia (AML) cell lines. Further investigation suggested that enhanced oncolytic effect of MM was due to increased apoptosis induction. In an U937 xenograft AML mouse model, MM displayed greater tumor suppression and prolonged survival. Furthermore, MM efficiently killed blasts from 16 out of 20 AML patients and elicited more efficient killing effect on 11 patients when co-administered with Ara-C. Our results demonstrate that MM is a promising therapeutic candidate for hematological malignancies.

Keywords: Acute myeloid leukemia; Measles virus; Mumps virus; Oncolytic virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Chlorocebus aethiops
Cytopathogenic Effect, Viral
Humans
Jurkat Cells
Leukemia, Myeloid, Acute / therapy*
Leukemia, Myeloid, Acute / virology*
Male
Measles virus / immunology
Measles virus / physiology*
Mice
Mice, Inbred BALB C
Mice, Nude
Mumps virus / immunology
Mumps virus / physiology*
Oncolytic Virotherapy / methods*
U937 Cells
Vero Cells
Xenograft Model Antitumor Assays