897-D Combinational treatment of reovirus and NK cells against bladder cancer cells using an intravesical therapy mimicking in vitro assay
Bibliographic record
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".