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Abstract
Background A variety of combination treatments have been investigated to overcome the low response rate and potential resistance of bladder cancer.1 Reovirus, one of the oncolytic viruses, has been studied for bladder cancer cells (BCC). While intravesical treatment with Reovirus serves as an efficient strategy, its monotherapy has often shown modest cytotoxicity against some BCC.2 Considering that natural killer (NK) cells have emerged as a key player in BC immunotherapy,3 4 it remains clear that a combination of reovirus with NK cells will be necessary to optimize therapeutic efficacy.
Methods We here investigated the anti-tumor effects of mono treatment and combination treatment at various concentrations in three types of BCC lines (5637, HT-1376, 253J-BV) using an in vitro experimental model mimicking intravesical therapy. To simulate the clinical treatment, we reduced the cytotoxicity duration to 2 hours followed by washing. In contrast, to enhance the anti-tumor effect, we utilized RP116, which is an attenuated reovirus with natural truncation of sigma 1, and interleukin (IL) 18/21-treated NK (eNK) cells expanded under stimulation with K562-mbIL-18/21 feeder cells and IL-2 and IL-15 from peripheral blood.
Results Monotherapy of RP116 or IL18/21-treated eNK cells exhibited effective cytotoxicity against the 5637 (grade 1 carcinoma), but not against HT-1376 (grade 2 carcinoma) and 253J-BV (derived from a metastatic site). However, combinational treatment of IL18/21-treated eNK cells and RP116 showed effective cytotoxicity against HT-1376 and 253J-BV.
Conclusions Based on these findings, the combination therapy involving reovirus and NK cells could serve as an effective treatment strategy for bladder cancer.
References
Peng, Mei, et al. Novel combination therapies for the treatment of bladder cancer. Front.Oncol. 2021;10
Vidal, Laura, et al. A phase I study of intravenous oncolytic reovirus type 3 Dearing in patients with advanced cancer. Clin Cancer Res. 2008;14:7127–37
Thangaraj, Jaya Lakshmi, et al. Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21. Cancer Immunol Immunother 2022;71(3):613–625
Bae, Woo Kyun, et al. A phase I study of locoregional high-dose autologous natural killer cell therapy with hepatic arterial infusion chemotherapy in patients with locally advanced hepatocellular carcinoma. Front. Immunol. 2022;13:879452
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