Enhanced antitumor effects of an engineered measles virus Edmonston strain expressing the wild-type N, P, L genes on human renal cell carcinoma.
Measles virus Edmonston strain (MV-Edm) is thought to have remarkable oncolytic activity that selectively destroys human tumor cells. The P/V/C protein of wild-type MV was shown to resist the antiviral effects of interferon (IFN)-alpha. Here, we engineered new MVs by arming MV-Edm tag strain (a V-defective vaccine-lineage strain, MV-Etag) with the P or N, P, and L genes of wild-type MV (MV-P and MV-NPL, respectively). The oncolytic activities of the MVs were determined in human renal cell carcinoma (RCC) cell lines and primary human RCC cells by the MTT assay. The antitumor efficacy of the MVs was evaluated in A-498 xenografts in nude mice. IFN-alpha effectively inhibited the replication of MV-Etag and MV-P, but not MV-NPL. MV-NPL more efficiently induced cytopathic effects (CPEs) in OS-RC-2 cells, even in the presence of human IFN-alpha. MV-NPL replicated more rapidly than MV-P and MV-Etag in A-498 cells. Apoptosis was induced earlier in A-498 cells by MV-NPL than MV-Etag and MV-P. MV-NPL showed more significant antitumoral effects and had prolonged replication compared to MV-Etag and MV-P. In this study, we demonstrated that the newly engineered MV-NPL has more effective oncolytic activity and may help establish an innovative cancer therapy.
Meng
Xin
X
Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Nakamura
Takafumi
T
Okazaki
Toshihiko
T
Inoue
Hiroyuki
H
Takahashi
Atsushi
A
Miyamoto
Shohei
S
Sakaguchi
Gaku
G
Eto
Masatoshi
M
Naito
Seiji
S
Takeda
Makoto
M
Yanagi
Yusuke
Y
Tani
Kenzaburo
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D007680:Kidney Neoplasms / Q000628:therapy*; D008458:Measles Vaccine / Q000235:genetics*; D008459:Measles virus / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy / Q000379:methods
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D008458:Measles Vaccine