Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

The Effects of Mesenchymal Stem Cells Loaded with Oncolytic Coxsackievirus A21 on Mouse Models of Colorectal Cancer

Author(s): Reza Karbalaee, Saber Mehdizadeh, Hadi Esmaeili Gouvarchin Ghaleh*, Morteza Izadi, Bahman Jalali Kondori, Ruhollah Dorostkar and Seyed Morteza Hosseini

Volume 24, Issue 9, 2024

Published on: 02 February, 2024

Page: [967 - 974] Pages: 8

DOI: 10.2174/0115680096273465231201115839

Price: $65

conference banner
Abstract

Background: Cancer is a major cause of death worldwide. Colorectal cancer is the second most common type. Additional treatments like chemotherapy and radiation therapy may be recommended. Developing new techniques is vital due to drug resistance and a lack of targeted therapies.

Objective: In this study, the effects of mesenchymal stem cells (MSCs) loaded with oncolytic Coxsackievirus A21 (CVA21) on a mouse model of CRC were investigated.

Methods: The therapeutic potency of MSCs loaded with oncolytic CVA21 were evaluated in an experimental mouse model of colorectal cancer which received an injection CT26 cells per mouse subcutaneously. Splenocyte proliferation index, lactate dehydrogenase (LDH) assay, nitric oxide (NO) production assessment, and cytokine assay (IFN-γ, IL-4, IL-10, and TGF-β) in the splenocyte supernatant were all used to evaluate the impact of MSCs loaded with CVA21.

Results: The results of this study showed that the treatment of a mouse model of colorectal cancer with MSCs loaded with oncolytic CVA21 could significantly suppress the tumor growth, which was accompanied by stimulation of splenocytes proliferation index, an increase of NO and LDH. Also, MSCs loaded with oncolytic CVA21 increased the secretion of IFN-γ and decreased the secretion of IL-4, IL-10, and TGF-β.

Conclusion: The results of the current study suggest that MSCs loaded with oncolytic CVA21 therapy for the CRC mouse model may have some potential advantages. On the other hand, the results of the study showed that, in addition to activating the acquired immune system, the use of MSCs loaded with oncolytic CVA21 also stimulates the innate immune system by increasing level of nitric oxide.

Keywords: Anti-tumor immunity, colorectal cancer, mesenchymal stem cells, CT26 cell line, mouse model, Coxsackievirus A21, oncolytic virus.

« Previous Next »
Graphical Abstract

[1]
Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer, 2019, 144(8), 1941-1953.
[http://dx.doi.org/10.1002/ijc.31937] [PMID: 30350310]
[2]
Bray, F. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2020, 70(4), 313-313.
[http://dx.doi.org/10.3322/caac.21609]
[3]
Cheng, L.; Eng, C.; Nieman, L.Z.; Kapadia, A.S.; Du, X.L. Trends in colorectal cancer incidence by anatomic site and disease stage in the United States from 1976 to 2005. Am. J. Clin. Oncol., 2011, 34(6), 573-580.
[http://dx.doi.org/10.1097/COC.0b013e3181fe41ed] [PMID: 21217399]
[4]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[5]
Bailey, C.E.; Hu, C.Y.; You, Y.N.; Bednarski, B.K.; Rodriguez-Bigas, M.A.; Skibber, J.M.; Cantor, S.B.; Chang, G.J. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg., 2015, 150(1), 17-22.
[http://dx.doi.org/10.1001/jamasurg.2014.1756] [PMID: 25372703]
[6]
Thanikachalam, K.; Khan, G. Colorectal cancer and nutrition. Nutrients, 2019, 11(1), 164.
[http://dx.doi.org/10.3390/nu11010164] [PMID: 30646512]
[7]
Arnold, M.; Sierra, M.S.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global patterns and trends in colorectal cancer incidence and mortality. Gut, 2017, 66(4), 683-691.
[http://dx.doi.org/10.1136/gutjnl-2015-310912] [PMID: 26818619]
[8]
Dolatkhah, R. Colorectal cancer in Iran: Molecular epidemiology and screening strategies. J. Cancer Epidemiol., 2015, 2015
[9]
Johdi, N.A.; Sukor, N.F. Colorectal cancer immunotherapy: Options and strategies. Front. Immunol., 2020, 11, 1624.
[http://dx.doi.org/10.3389/fimmu.2020.01624] [PMID: 33042104]
[10]
Chakrabarti, S.; Peterson, C.Y.; Sriram, D.; Mahipal, A. Early stage colon cancer: Current treatment standards, evolving paradigms, and future directions. World J. Gastrointest. Oncol., 2020, 12(8), 808-832.
[http://dx.doi.org/10.4251/wjgo.v12.i8.808] [PMID: 32879661]
[11]
Krasteva, N.; Georgieva, M. Promising therapeutic strategies for colorectal cancer treatment based on nanomaterials. Pharmaceutics, 2022, 14(6), 1213.
[http://dx.doi.org/10.3390/pharmaceutics14061213] [PMID: 35745786]
[12]
Kooti, W. Oncolytic Newcastle disease virus effects on immune response-a new issue in cancer treatment. Klin. Onkol., 2023, 36(2), 124-129.
[http://dx.doi.org/10.48095/ccko2023124]
[13]
Bradley, S.; Jakes, A.; Harrington, K.; Pandha, H.; Melcher, A.; Errington-Mais, F. Applications of coxsackievirus A21 in oncology. Oncolytic Virother., 2014, 3, 47-55.
[http://dx.doi.org/10.2147/OV.S56322] [PMID: 27512662]
[14]
Annels, N.E.; Arif, M.; Simpson, G.R.; Denyer, M.; Moller-Levet, C.; Mansfield, D.; Butler, R.; Shafren, D.; Au, G.; Knowles, M.; Harrington, K.; Vile, R.; Melcher, A.; Pandha, H. Oncolytic immunotherapy for bladder cancer using coxsackie A21 virus. Mol. Ther. Oncolytics, 2018, 9, 1-12.
[http://dx.doi.org/10.1016/j.omto.2018.02.001] [PMID: 29989024]
[15]
Moaven, O.; Mangieri, C.W.; Stauffer, J.A.; Anastasiadis, P.Z.; Borad, M.J. Strategies to develop potent oncolytic viruses and enhance their therapeutic efficacy. JCO Precis. Oncol., 2021, 5(5), 733-743.
[http://dx.doi.org/10.1200/PO.21.00003] [PMID: 34250395]
[16]
Wang, X.; Zhao, X.; He, Z. Mesenchymal stem cell carriers enhance anti-tumor efficacy of oncolytic virotherapy (Review). Oncol. Lett., 2021, 21(4), 238.
[http://dx.doi.org/10.3892/ol.2021.12499] [PMID: 33664802]
[17]
Mahasa, K.J.; de Pillis, L.; Ouifki, R.; Eladdadi, A.; Maini, P.; Yoon, A.R.; Yun, C.O. Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy. Sci. Rep., 2020, 10(1), 425.
[http://dx.doi.org/10.1038/s41598-019-57240-x] [PMID: 31949228]
[18]
Yoon, A.R.; Rivera-Cruz, C.; Gimble, J.M.; Yun, C.O.; Figueiredo, M.L. Immunotherapy by mesenchymal stromal cell delivery of oncolytic viruses for treating metastatic tumors. Mol. Ther. Oncolytics, 2022, 25, 78-97.
[http://dx.doi.org/10.1016/j.omto.2022.03.008] [PMID: 35434272]
[19]
Ghasemi Darestani, N.; Gilmanova, A.I.; Al-Gazally, M.E.; Zekiy, A.O.; Ansari, M.J.; Zabibah, R.S.; Jawad, M.A.; Al-Shalah, S.A.J.; Rizaev, J.A.; Alnassar, Y.S.; Mohammed, N.M.; Mustafa, Y.F.; Darvishi, M.; Akhavan-Sigari, R. Mesenchymal stem cell-released oncolytic virus: Asn innovative strategy for cancer treatment. Cell Commun. Signal., 2023, 21(1), 43.
[http://dx.doi.org/10.1186/s12964-022-01012-0] [PMID: 36829187]
[20]
Esmaili Gourvarchin Galeh, H.; Meysam Abtahi Froushani, S.; Afzale Ahangaran, N.; Hadai, S.N. Effects of educated monocytes with xenogeneic mesenchymal stem cell–derived conditioned medium in a mouse model of chronic asthma. Immunol. Invest., 2018, 47(5), 504-520.
[http://dx.doi.org/10.1080/08820139.2018.1458108] [PMID: 29671652]
[21]
Aindelis, G.; Tiptiri-Kourpeti, A.; Lampri, E.; Spyridopoulou, K.; Lamprianidou, E.; Kotsianidis, I.; Ypsilantis, P.; Pappa, A.; Chlichlia, K. Immune responses raised in an experimental colon carcinoma model following oral administration of Lactobacillus casei. Cancers, 2020, 12(2), 368.
[http://dx.doi.org/10.3390/cancers12020368] [PMID: 32033490]
[22]
Keshavarz, M.; Ebrahimzadeh, M.S.; Miri, S.M.; Dianat-Moghadam, H.; Ghorbanhosseini, S.S.; Mohebbi, S.R.; Keyvani, H.; Ghaemi, A. Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment. Virol. J., 2020, 17(1), 64.
[http://dx.doi.org/10.1186/s12985-020-01326-w] [PMID: 31906972]
[23]
Jafari, S.; Froushani, S.M.A.; Tokmachi, A. Combined extract of heated 4T1 and a heat-killed preparation of Lactobacillus casei in a mouse model of breast cancer. Iran. J. Med. Sci., 2017, 42(5), 457-464.
[PMID: 29234178]
[24]
Altun, İ.; Sonkaya, A. The most common side effects experienced by patients were receiving first cycle of chemotherapy. Iran. J. Public Health, 2018, 47(8), 1218-1219.
[PMID: 30186799]
[25]
Han, Y.; Yang, J.; Fang, J.; Zhou, Y.; Candi, E.; Wang, J.; Hua, D.; Shao, C.; Shi, Y. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduct. Target. Ther., 2022, 7(1), 92.
[http://dx.doi.org/10.1038/s41392-022-00932-0] [PMID: 35314676]
[26]
Au, G.G.; Beagley, L.G.; Haley, E.S.; Barry, R.D.; Shafren, D.R. Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18. Virol. J., 2011, 8(1), 22.
[http://dx.doi.org/10.1186/1743-422X-8-22] [PMID: 21241513]
[27]
Andtbacka, R.H.I.; Curti, B.; Daniels, G.A.; Hallmeyer, S.; Whitman, E.D.; Lutzky, J.; Spitler, L.E.; Zhou, K.; Bommareddy, P.K.; Grose, M.; Wang, M.; Wu, C.; Kaufman, H.L. Clinical responses of oncolytic coxsackievirus A21 (V937) in patients with unresectable melanoma. J. Clin. Oncol., 2021, 39(34), 3829-3838.
[http://dx.doi.org/10.1200/JCO.20.03246] [PMID: 34464163]
[28]
Kingston, J.A. The Efficacy of Coxsackievirus A21 in Combination with Radiotherapy for the Treatment of Colorectal Cancer; University of Leeds, 2022.
[29]
Au, G.; Lindberg, A.; Barry, R.; Shafren, D. Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21. Int. J. Oncol., 2005, 26(6), 1471-1476.
[http://dx.doi.org/10.3892/ijo.26.6.1471] [PMID: 15870858]
[30]
Shafren, D.R.; Au, G.G.; Nguyen, T.; Newcombe, N.G.; Haley, E.S.; Beagley, L.; Johansson, E.S.; Hersey, P.; Barry, R.D. Systemic therapy of malignant human melanoma tumors by a common cold-producing enterovirus, coxsackievirus A21. Clin. Cancer Res., 2004, 10(1), 53-60.
[http://dx.doi.org/10.1158/1078-0432.CCR-0690-3] [PMID: 14734451]
[31]
Choi, S.; Hong, J.A.; Choi, H.J.; Song, J.J. Enhanced tumor targeting and timely viral release of mesenchymal stem cells/oncolytic virus complex due to GRP78 and inducible E1B55K expressions greatly increase the antitumor effect of systemic treatment. Mol. Ther. Oncolytics, 2022, 27, 26-47.
[http://dx.doi.org/10.1016/j.omto.2022.09.004] [PMID: 36247810]
[32]
Mirlekar, B. Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy. SAGE Open Med., 2022, 10, 20503121211069012.
[http://dx.doi.org/10.1177/20503121211069012] [PMID: 35096390]
[33]
Jorgovanovic, D.; Song, M.; Wang, L.; Zhang, Y. Roles of IFN-γ in tumor progression and regression: A review. Biomark. Res., 2020, 8(1), 49.
[http://dx.doi.org/10.1186/s40364-020-00228-x] [PMID: 33005420]

Rights & Permissions Print Cite
Article Metrics
33
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy