Article Text

Download PDFPDF

897-D Combinational treatment of reovirus and NK cells against bladder cancer cells using an intravesical therapy mimicking in vitro assay
  1. Yuree Lim1,
  2. Jeehun Park2,
  3. Joung Eun Lim3,
  4. Minji Park4,
  5. Seung Kwon Koh4,
  6. Mijeong Lee4,
  7. Sang-ki Kim5,
  8. Seung-Hwan Lee6,
  9. Ki-Hoon Song7,
  10. Dong Guk Park7,8,
  11. Byong Chang Jeong3,4 and
  12. Duck Cho4
  1. 1Sungkyunkwan University, Suwon, Republic of Korea
  2. 2Seoul National University, Seoul Republic of Korea
  3. 3Samsung Medical Center, Seoul, Republic of Korea
  4. 4SungKyunKwan University, Seoul, Republic of Korea
  5. 5Kongju National University, Yesan, Korea, Republic of Korea
  6. 6University of Ottawa, Ottawa, ON, Canada
  7. 7ViroCure Inc., Seoul, Republic of Korea
  8. 8Dankook University, Cheonan, Republic of Korea
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


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.


  1. Peng, Mei, et al. Novel combination therapies for the treatment of bladder cancer. Front.Oncol. 2021;10

  2. 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

  3. 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

  4. 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

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.