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Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain

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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.

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Authors and Affiliations

  1. Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan

    Ayako Takenouchi, Kengo Saito, Eriko Saito & Hiroshi Shirasawa

  2. Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan

    Ayako Takenouchi, Eriko Saito, Takeshi Saito, Tomoro Hishiki, Tadashi Matsunaga, Hideo Yoshida & Naomi Ohnuma

  3. Laboratory Animal Center, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan

    Naohisa Isegawa

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  1. Ayako Takenouchi
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  2. Kengo Saito
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Correspondence to Hiroshi Shirasawa.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Ethics Committee of Chiba University. This article does not contain any studies with human participants performed by any of the authors.

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Takenouchi, A., Saito, K., Saito, E. et al. Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain. Pediatr Surg Int 31, 1151–1159 (2015). https://doi.org/10.1007/s00383-015-3784-y

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