Volume 29, Issue 1 And 2 (1-2025)                   IBJ 2025, 29(1 And 2): 9-19 | Back to browse issues page

Ethics code: IR.PII.REC.1398.009


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Jafari M, Abdoli S, Asgari M, Moghaddam Pour M, Shokrgozar M A, Sharifzadeh Z. Combination Therapy of Oncolytic Newcastle Virus and Lenalidomide Enhanced Cytotoxicity in Prostate Cancer Cells. IBJ 2025; 29 (1 and 2) :9-19
URL: http://ibj.pasteur.ac.ir/article-1-4367-en.html
Abstract:  
Background: Despite existing treatments, advanced solid tumors, such as prostate cancer (PCa), require the development of novel anticancer therapies. Oncolytic viruses (OVs) present a potential treatment option for solid tumors. Newcastle disease virus (NDV) is one of the most promising OVs that can replicate within and destroys human cancer cells. This study aimed to evaluate the cytotoxic and apoptotic effects of the NDV strain on human PCa cells in vitro. Additionally, We examined a novel treatment for PCa by combining Lenalidomide (Len) with NDV.
Methods: NDV strains La Sota, B1, and I2 were tested for cytotoxicity against several cell lines. A safety assessment was conducted in primary cells using peripheral blood mononuclear cells (PBMCs). Also, apoptosis induction was measured using annexin V/7AAD staining. Finally, the cytotoxic effects of NDV alone and in combination with Len, were assessed using MTT.
Results: The NDV showed cytotoxic effects on tumor cell lines and induced apoptosis in infected prostate cells compared to control cells. The NDV La Sota strain exhibited significant oncolytic capacity, reducing the viability of LNCaP and DU145 cells to less than 40% at specific concentrations, while showing no cytotoxic effects on primary PBMCs. Also, NDV induced apoptosis in the prostate cell line by 60%. Furthermore, Len enhanced the cytotoxicity of PCa cells when combined with NDV.
Conclusion: Our study confirms the efficacy of oncolytic NDV treatment for PCa, particularly utilizing the La Sota strain. When combined with Len, NDV indicates an enhanced effectiveness in destroying tumor cells. These findings suggest a prospective treatment approach that needs more preclinical and clinical studies to improve outcomes in PCa treatment.
Type of Study: Full Length/Original Article | Subject: Cancer Biology

References
1. Barsouk A, Padala SA, Vakiti A, Mohammed A, Saginala K, Thandra KC, et al. Epidemiology, staging and management of prostate cancer. Med Sci. 2020;8(3):28. [DOI:10.3390/medsci8030028]
2. Sekhoacha M, Riet K, Motloung P, Gumenku L, Adegoke A, Mashele S. Prostate cancer review: Genetics, diagnosis, treatment otions, and alternative approaches. Molecules. 2022;27(17):5730. [DOI:10.3390/molecules27175730]
3. Liang H, Liu Y, Guo J, Dou M, Zhang X, Hu L, et al. Progression in immunotherapy for advanced prostate cancer. Front Oncol. 2023;13:1126752. [DOI:10.3389/fonc.2023.1126752]
4. Kocic G, Hadzi-Djokic J, Simic T. Prostate cancer: advancements in the pathogenesis, diagnosis and personalized therapy. Springer Nature. 2024: 325-33. [DOI:10.1007/978-3-031-51712-9]
5. Jafari M, Kadkhodazadeh M, Shapourabadi MB, Goradel NH, Shokrgozar MA, Arashkia A, et al. Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses. Front Immunol. 2022;13:1012806. [DOI:10.3389/fimmu.2022.1012806]
6. Li Y, Duan HY, Yang K-D, Ye JF. Advancements and challenges in oncolytic virus therapy for gastrointestinal tumors. Biomed Pharmacother. 2023;168:115627. [DOI:10.1016/j.biopha.2023.115627]
7. Meyers DE, Thakur S, Thirukkumaran CM, Morris DG. Oncolytic virotherapy as an immunotherapeutic strategy for multiple myeloma. Blood Cancer J. 2017;7(12):640. [DOI:10.1038/s41408-017-0020-0]
8. Yang K, Feng S, Luo Z. Oncolytic adenovirus, a new treatment strategy for prostate cancer. Biomedicines. 2022;10(12):3262. [DOI:10.3390/biomedicines10123262]
9. Muthukutty P, Yoo SY. Oncolytic virus engineering and utilizations: Cancer immunotherapy perspective. Viruses. 2023;15(8):1645. [DOI:10.3390/v15081645]
10. Jafari M, Maali A, Shokrgozar MA, Sharifzadeh Z. Nanobody-based cancer immunotherapy and immunoimaging. Front Immunol. 2023;14:1213386. [DOI:10.3389/fimmu.2023.1213386]
11. Blesa JMG, Godoy MP, Esparcia MF, Mollá SB, Magán BM, Ortells JMS, et al. PSA response to Lenalidomide therapy in a pre-treated patient with metastatic prostate cancer refractory to hormones and chemotherapy: A case report. Case Rep Oncol. 2012;5(1):181-6. [DOI:10.1159/000336481]
12. Jafari M, Moghaddam Pour M, Taghizadeh M, Masoudi S, Bayat Z. Comparative assessment of humoral immune responses of aluminum hydroxide and oil-emulsion adjuvants in Influenza (H9N2) and Newcastle inactive vaccines to chickens. Artif Cells Nanomed Biotechnol. 2017;45(1):84-9. [DOI:10.3109/21691401.2015.1129626]
13. Shobana R, Samal SK, Elankumaran S. Prostate-specific antigen-retargeted recombinant newcastle disease virus for prostate cancer virotherapy. J Virol. 2013;87(7):3792-800. [DOI:10.1128/JVI.02394-12]
14. Elankumaran S. Genetically engineered Newcastle disease virus for prostate cancer: A magic bullet or a misfit. Expert Rev Anticancer Ther. 2013;13(7):769-72. [DOI:10.1586/14737140.2013.811062]
15. Wang X, Shao X, Gu L, Jiang K, Wang S, Chen J, et al. Targeting STAT3 enhances NDV-induced immunogenic cell death in prostate cancer cells. J Cell Mol Med. 2020;24(7):4286-97. [DOI:10.1111/jcmm.15089]
16. Yeşilaltay A, Muz D, Erdal B, Bilgen T, Batar B, Turgut B, et al. Myxoma virus combination therapy enhances lenalidomide and bortezomib treatments for multiple myeloma. Pathogens. 2024;13(1):72. [DOI:10.3390/pathogens13010072]
17. McAusland TM, Van Vloten JP, Santry LA, Guilleman MM, Rghei AD, Ferreira EM, et al. Combining vanadyl sulfate with Newcastle disease virus potentiates rapid innate immune-mediated regression with curative potential in murine cancer models. Mol Ther Oncolytics. 2021;20:306-24. [DOI:10.1016/j.omto.2021.01.009]
18. Zeldis JB, Knight R, Hussein M, Chopra R, Muller G. A review of the history, properties, and use of the immunomodulatory compound lenalidomide. Ann N Y Acad Sci. 2011;1222(1):76-82. [DOI:10.1111/j.1749-6632.2011.05974.x]
19. Zhu D, Corral LG, Fleming YW, Stein B. Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation. Cancer Immunol Immunother. 2008;57(12):1849-59. [DOI:10.1007/s00262-008-0512-7]
20. Wang J, McGuire TR, Britton H, Schwarz JK, Loberiza F, Meza JL, et al. Lenalidomide and cyclophosphamide immunoregulation in patients with metastatic, castration-resistant prostate cancer. Clin Exp Metastasis. 2015;32(2):111-24. [DOI:10.1007/s10585-015-9696-3]
21. Henry JY, Lu L, Adams M, Meyer B, Bartlett B, Dalgleish AG, et al. Lenalidomide enhances the anti-prostate cancer activity of docetaxel in vitro and in vivo. Prostate. 2012;72(8):856-67. [DOI:10.1002/pros.21488]
22. Shimokihara K, Kawahara T, Suzuki T, Mochizuki T, Takamoto D, Teranishi JI, et al. Lenalidomide decreased the PSA level for castration‐resistant prostate cancer: A case report. Clin Case Rep. 2018;6(2):391-4. [DOI:10.1002/ccr3.1328]
23. Marschner N, Zaiss M. Long-term disease stabilization in a patient with castration-resistant metastatic prostate cancer by the addition of lenalidomide to low-dose dexamethasone and celecoxib. Onkologie. 2012;35(5):279-82. [DOI:10.1159/000337403]
24. Sundaresan L, Kumar P, Chatterjee S. Mechanistic insights into the differential effects of thalidomide and lenalidomide in metastatic prostate cancer. Future Oncol. 2018;14(23):2383-401. [DOI:10.2217/fon-2018-0090]
25. Yurchenko KS, Jing Y, Shestopalov AM. Adaptation of the newcastle disease virus to cell cultures for enhancing its oncolytic properties. Acta Naturae. 2019;11(1):66-73. [DOI:10.32607/20758251-2019-11-1-66-73]
26. Ali AA, Halldén G. Development of oncolytic adenoviruses for the management of prostate cancer. Prostate Cancer. 2018;10(5):73515. [DOI:10.5772/intechopen.73515]
27. Van de Merbel M, van der Horst G, van der Mark MH, Bots ST, van den Wollenberg D, de Ridder CM, et al. Reovirus mutant jin-3 exhibits lytic and immune-stimulatory effects in preclinical human prostate cancer models. Cancer Gene Therapy. 2022;29(1):1-10. [DOI:10.1038/s41417-021-00360-2]
28. Tolcher AW, Victoria I, Germann N, Luecke S, Bailey M, Kordes M. Phase I, open-label, dose-escalation trial investigating the safety and efficacy of oncolytic virus BI 1821736 in patients with advanced solid tumors. J Clin Oncol. 2024;42(16):2688. [DOI:10.1200/JCO.2024.42.16_suppl.TPS2688]
29. Yurchenko KS, Zhou P, Kovner AV, Zavjalov EL, Shestopalova LV, Shestopalov AM. Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model. Plos one. 2018;13(4):e0195425. [DOI:10.1371/journal.pone.0195425]
30. Ginting TE, Suryatenggara J, Christian S, Mathew G. Proinflammatory response induced by Newcastle disease virus in tumor and normal cells. Oncolytic Virother. 2017;6:21-30. [DOI:10.2147/OV.S123292]
31. Mao LJ, Kan Y, Li BH, Ma S, Liu Y, Yang DL, et al. Combination therapy of prostate cancer by oncolytic adenovirus harboring interleukin 24 and ionizing radiation. Front Oncol. 2020;10:421. [DOI:10.3389/fonc.2020.00421]
32. Ginting TE, Hidayat NR, Cornelia V, Larasati YO, Zarkasie K, Yusuf I. Oncolytic Newcastle disease virus enhanced apoptosis in colorectal cancer cell lines. BioRxiv. 2023;16:537098. [DOI:10.1101/2023.04.16.537098]
33. Elankumaran S, Rockemann D, Samal SK. Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death. J Virol. 2006;80(15):7522-34. [DOI:10.1128/JVI.00241-06]
34. Mansour M, Palese P, Zamarin D. Oncolytic specificity of Newcastle disease virus is mediated by selectivity for apoptosis-resistant cells. J Virol. 2011;85(12):6015-23. [DOI:10.1128/JVI.01537-10]
35. Song KY, Wong J, Gonzalez L, Sheng G, Zamarin D, Fong Y. Antitumor efficacy of viral therapy using genetically engineered Newcastle disease virus [NDV (F3aa)-GFP] for peritoneally disseminated gastric cancer. J Mol Med. 2010;88(6):589-96. [DOI:10.1007/s00109-010-0605-6]
36. Kalantari A, Farashi Bonab S, Keyvanfar H, Mortazavi P. Evaluation of apoptosis induction by Newcastle disease virus lasota strain in human breast carcinoma cells. Arch Razi Inst. 2020;75(3):367-76.
37. Keizman D, Zahurak M, Sinibaldi V, Carducci M, Denmeade S, Drake C, et al. Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: results of a phase I/II double-blinded, randomized study. Clin Cancer Res. 2010;16(21):5269-76. [DOI:10.1158/1078-0432.CCR-10-1928]
38. Madan RA, Karzai FH, Ning YM, Adesunloye BA, Huang X, Harold N, et al. Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration-resistant prostate cancer. BJU Int. 2016;118(4):590-7. [DOI:10.1111/bju.13412]
39. Xing DL, Song DK, Zhang LR. Lenalidomide in treating patients with castration-resistant prostate cancer. Asian Pac J Cancer Prev. 2015;16(9):3969-72. [DOI:10.7314/APJCP.2015.16.9.3969]
40. Ganesan S, Palani HK, Balasundaram N, David S, Devasia AJ, George B, et al. Combination Lenalidomide/Bortezomib Treatment Synergistically Induces Calpain-Dependent Ikaros Cleavage and Apoptosis in Myeloma Cells. Mol Cancer Res. 2020;18(4):529-36. [DOI:10.1158/1541-7786.MCR-19-0431]
41. Zhou L. Caspase-8: Friend or foe in bortezomib/lenalidomide-based therapy for myeloma. Front Oncol. 2022;12:861709. [DOI:10.3389/fonc.2022.861709]
42. Zhou L, Huang X, Niesvizky R, Pu Z, Xu G. Caspase-8 regulates the antimyeloma activity of bortezomib and lenalidomide. J Pharmacol Exp Ther. 2021;379(3):303-9. [DOI:10.1124/jpet.121.000818]
43. Qu Z, Jiang C, Wu J, Ding Y. Lenalidomide induces apoptosis and inhibits angiogenesis via caspase‑3 and VEGF in hepatocellular carcinoma cells. Mol Med Rep. 2016;14(5):4781-6. [DOI:10.3892/mmr.2016.5797]
44. Nawrocki ST, Olea J, Villa Celi C, Dadrastoussi H, Wu K, Tsao-Wei D, et al. Comprehensive single-cell immune profiling defines the patient multiple myeloma microenvironment following oncolytic virus therapy in a phase Ib trial. Clin Cancer Res. 2023;29(24):5087-103. [DOI:10.1158/1078-0432.CCR-23-0229]

Add your comments about this article : Your username or Email:
CAPTCHA

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2025 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb