Oncolytic Viral Therapy for Neuroblastoma Cells with Sindbis Virus AR339 Strain

Overview

Journal Pediatr Surg Int

Specialties General Surgery
Pediatrics

Date 2015 Aug 24

PMID 26298056

Citations 8

Authors

Ayako Takenouchi

Kengo Saito

Eriko Saito

Takeshi Saito

Tomoro Hishiki

Tadashi Matsunaga

Naohisa Isegawa

Hideo Yoshida

Naomi Ohnuma

Hiroshi Shirasawa

Affiliations

Soon will be listed here.

Abstract

Purpose: With current treatment regimens, high-risk neuroblastoma (NB) remains largely incurable. Oncolytic viral therapy uses replication-competent viruses, like Sindbis virus (SINV), to kill cancers. The SINV AR339 strain is blood borne and relatively non-virulent. We evaluated the feasibility of SINV AR339 for treating human NB.

Methods: The cytotoxicity and viral growth of SINV AR339 were evaluated for five human NB cell lines, SK-N-SH, IMR-32, LAN-5, GOTO, and RT-BM-1. SINV-induced apoptosis was confirmed by TUNEL assays and PARP-1 cleavage. In vivo effects of SINV on neuroblastoma cell xenografts in nude mice were assessed by intratumoral or intravenous SINV inoculation.

Results: In five human NB cell lines, SINV infections induced remarkable cytotoxicity. The mRNA expressions of anti-apoptotic genes, Bcl-2 and Bcl-xL, in LAN-5 and RT-BM-1, which were less sensitive to SINV infection, increased in response to SINV infection, while the other NB cell lines sensitive to SINV infection failed to respond. In nude mice, intratumoral and intravenous SINV inoculations caused significant regression of NB xenograft tumors.

Conclusion: Our results suggested that SINV AR339 was significantly oncolytic against human NB. Thus, SINV showed promise as a novel therapy for treating NB.

Citing Articles

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