Abstract 2617
Background
The high prevalence and poor prognosis of prostate cancer provides a strong rationale for developing new treatment strategies. Reovirus, a double-stranded RNA virus, preferentially kills a variety of cancer cells including those of prostate, breast and brain and have been studied in multiple clinical trials. In this study, we examine the oncolytic activity of reovirus and its potential as a therapeutic agent for human prostate cancer cell lines, with particular focus on the highly metastatic patient’s derived cell.
Methods
We used hormone-sensitive LNCaP cells, hormone-insensitive 22Rv1 cells, and castration resistant prostate cancer (CRPC) patient-derived primary cells. We analyzed in vitro anti-cancer effect of reovirus using real-time quantitative reverse transcription-PCR, western blotting, annexin V/propidium iodide assay and CellTiter Glo® luminescent assay. The murine TRAMP-C1 syngeneic and human 22Rv1 and patient-derived xenograft model was employed to evaluate in vivo efficacy. Statistical evaluation of the results was performed by one-way ANOVA.
Results
Reovirus significantly reduced cell viability in both androgen-sensitive LNCaP and androgen-insensitive 22Rv1 cells. The apoptosis induced by reovirus was associated with cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP) and increased annexin V-positive cells. Reovirus reduced expression of AR, AR splice variant 7 (AR-V7) and prostate specific antigen (PSA) in LNCaP and 22Rv1 cells. The treatment of reovirus inhibited the growth of TRAMP-C1, 22Rv1 and CRPC mouse model in vivo.
Conclusions
Taken together, our results show that reovirus has a strong anti-tumor effect in prostate cancer cells including CRPC in vitro and in vivo. It can be a promising virus-associated agent in the anticancer treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2018R1D1A1B01040663).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5650 - Tissue-based activation of mucosal-associated invariant T (MAIT) cells in combination ipilimumab and nivolumab checkpoint inhibitor (CI) colitis.
Presenter: Sarah Sasson
Session: Poster Display session 3
Resources:
Abstract
5944 - Significance of severe immune-related adverse effects (irAE) on patients with advanced tumors treated with immune checkpoint inhibitors being admitted for secondary toxicity: Clinical relevance and next steps
Presenter: Leyre Zubiri
Session: Poster Display session 3
Resources:
Abstract
5989 - Implementation of a dedicated immuno-oncology toxicity service reduces the acute impact of immune-related adverse events
Presenter: Anna Olsson-Brown
Session: Poster Display session 3
Resources:
Abstract
3267 - Cardiotoxic and pro-inflammatory effects induced by the association of immune checkpoint inhibitor Pembrolizumab and Trastuzumab in preclinical models
Presenter: Nicola Maurea
Session: Poster Display session 3
Resources:
Abstract
3417 - Interstitial lung disease associated with immune-checkpoint inhibitors in malignant diseases
Presenter: Akira Yamagata
Session: Poster Display session 3
Resources:
Abstract
2071 - A Phase 1 Study of Intraperitoneal MCY-M11 Anti-Mesothelin CAR for Women with Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube, or Subjects with Peritoneal Mesothelioma with Recurrence after Prior Chemotherapy
Presenter: Christina Annunziata
Session: Poster Display session 3
Resources:
Abstract
4935 - Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumors (IMCnyeso-101)
Presenter: Juanita Lopez
Session: Poster Display session 3
Resources:
Abstract
5613 - Nimotuzumab-Cisplatin-Radiation versus Cisplatin-Radiation in HPV negative oropharyngeal cancer
Presenter: Kumar Prabhash
Session: Poster Display session 3
Resources:
Abstract
2576 - Interim analysis of a single arm phase 2 study of adjuvant nivolumab after salvage resection in head and neck squamous cell carcinoma patients previously treated with definitive therapy.
Presenter: Trisha Wise-draper
Session: Poster Display session 3
Resources:
Abstract
4758 - A Phase I Study of the CDK4/6 Inhibitor, Palbociclib in combination with Cetuximab and Intensity Modulated Radiation Therapy (IMRT) for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN); A Result of Dose Escalation Cohort
Presenter: Nuttapong Ngamphaiboon
Session: Poster Display session 3
Resources:
Abstract