作者: Yang, An-Dao ; Giraldo, Carlos Rios ; Lee, Yeon-Sook ; Pashangzadeh, Salar ; Lee, So Hyun ; Song, Ki-Hoon ; Park, Dong Guk ; Alain, Tommy ; Enkhtaivan, Gansukh ; Cho, Nam-Hyuk ; Sharifi, Negar ; Jeong, Yeo Jin ; Hoang, Huy-Dung ; Woo, Jong Kyu ; Lee, You-Rim ; Xiang, Xiao

The mammalian reovirus Type 3 Dearing (T3D) is a naturally occurring oncolytic virus. We previously identified a T3D variant isolated from persistently infected cancer cells that has a premature stop codon mutation in the S1 gene, generating a truncated σ1-attachment protein that lacks the globular head. We now report on the molecular characterization of this variant, named RP116, and assess its antitumor potential in human cancer cells and syngeneic mouse models. RP116 replicates efficiently in several cancer cell lines, shows reduced dependency for the JAM-A receptor, significantly decreases tumor growth in syngeneic models when injected either intratumorally or intravenously, and generates long-term cures and immune memory in combination with checkpoint inhibitors. Finally, we demonstrate that RP116 infection in mice leads to reduced production of neutralizing antibodies directed against reovirus T3D, preserving the efficacy of subsequent reovirus treatment. These results establish the value of developing RP116 as an additional oncolytic reovirus platform.

Scientific Reports

Evaluating a combination treatment of NK cells and reovirus against bladder cancer cells using an in vitro assay to simulate intravesical therapy

Article

作者: Park, Minji ; Song, Ki-Hoon ; Park, Jeehun ; Park, Dong Guk ; Lim, Joung Eun ; Kim, Hyun-Young ; Cho, Duck ; Jeong, Byong Chang ; Lee, Seung-Hwan ; Lim, Yuree ; Lee, Mijeong ; Kim, Sang-Ki ; Koh, Seung Kwon

AbstractIntravesical treatment using either reovirus or natural killer (NK) cells serves as an efficient strategy for the treatment of bladder cancer cells (BCCs); however, corresponding monotherapies have often shown modest cytotoxicity. The potential of a locoregional combination using high-dose reovirus and NK cell therapy in an intravesical approach has not yet been studied. In this study, we evaluated the effectiveness of reoviruses and expanded NK cells (eNK) as potential strategies for the treatment of bladder cancer. The anti-tumor effects of mono-treatment with reovirus type 3 Dearing strain (RC402 and RP116) and in combination with interleukin (IL)-18/-21-pretreated eNK cells were investigated on BCC lines (5637, HT-1376, and 253J-BV) using intravesical therapy to simulate in vitro model. RP116 and IL-18/-21-pretreated eNK cells exhibited effective cytotoxicity against grade 1 carcinoma (5637 cells) when used alone, but not against HT-1376 (grade 2 carcinoma) and 253J-BV cells (derived from a metastatic site). Notably, combining RP116 with IL-18/-21-pretreated eNK cells displayed effective cytotoxicity against both HT-1376 and 253J-BV cells. Our findings underscore the potential of a combination therapy using reoviruses and NK cells as a promising strategy for treating bladder cancer.

100 项与 RP-116 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
黑色素瘤	临床前	韩国	ViroCure, Inc.初创企业	2023-09-13
唾液腺肿瘤	临床前	韩国	ViroCure, Inc.初创企业	2023-09-13
肉瘤	临床前	韩国	ViroCure, Inc.初创企业	2023-09-13