Evaluation of antitumor activity in strains of a new rotavirus group in Reoviridae family on a model of transplantable murine melanoma

The purpose was to study antitumor effects of the group K rotaviruses strains No. 228 and No. 100 in the experiment on a model of transplantable murine melanoma. Material and methods. The study included 65 С57Black/6 mice with transplantable B16/F10 melanoma and two strains of the Reoviridae family members characterized as rotaviruses, not belonging to the known groups, with the working title “group K rotaviruses (RVK)”. Animals received RVK in “vaccination” (before tumor transplantation) and “treatment” (after tumor formation) modes. Live and inactivated strains were used. RVK were administered intramuscularly as 0.3 ml of virus-containing culture fluid with at least 5x109 viral particles per 1 ml, with a total of 4 injections. Life span of mice and morphological characteristics of tumors were evaluated. Results. Injections of both strains increased the survival of tumor-bearing mice by 1.7-1.9 times in 4 of 8 experimental groups, compared to controls. The modes of RVK administration showed some differences: the survival was longer in mice with the “vaccination” mode compared to the “treatment” mode. Morphological changes in tumors were similar after application of both modes and inclued dystrophic changes of tumor cells, formation of extensive necrosis areas, and leukocyte infiltration. Discussion. Live and inactivated RVK had unidirectional effects implying its association with immunomodulatory action rather than with a direct lytic effect on the tumor. Conclusions. Both studied strains of rotaviruses in the group K had antitumor effect in the model of transplantable В16/F10 murine melanoma in the «vaccination» mode.

[1]  Y. Kodera,et al.  The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers , 2018, Cancers.

[2]  Pēteris Alberts,et al.  Long‐term treatment with the oncolytic ECHO‐7 virus Rigvir of a melanoma stage IV M1c patient, a small cell lung cancer stage IIIA patient, and a histiocytic sarcoma stage IV patient‐three case reports , 2016, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[3]  V. Schirrmacher.  Fifty Years of Clinical Application of Newcastle Disease Virus: Time to Celebrate! , 2016, Biomedicines.

[4]  C. Breitbach,et al.  Oncolytic Viruses: Therapeutics With an Identity Crisis , 2016, EBioMedicine.

[5]  F. Kühnel,et al.  Oncolytic Viruses as Anticancer Vaccines , 2014, Front. Oncol..

[6]  S. Workenhe,et al.  Oncolytic virotherapy and immunogenic cancer cell death: sharpening the sword for improved cancer treatment strategies. , 2014, Molecular therapy : the journal of the American Society of Gene Therapy.

[7]  D. Bartlett,et al.  Oncolytic viruses as therapeutic cancer vaccines , 2013, Molecular Cancer.

[8]  Derek L. Clouthier,et al.  Oncolytic vesicular stomatitis virus quantitatively and qualitatively improves primary CD8+ T-cell responses to anticancer vaccines , 2013, Oncoimmunology.

[9]  L. Zitvogel,et al.  Crosstalk between ER stress and immunogenic cell death. , 2013, Cytokine & growth factor reviews.

[10]  Laurence Zitvogel,et al.  Immunogenic cell death in cancer therapy. , 2013, Annual review of immunology.

[11]  M. Lotze,et al.  PAMPs and DAMPs: signal 0s that spur autophagy and immunity , 2012, Immunological reviews.

[12]  Songshu Meng,et al.  Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus replication , 2012, Archives of Virology.

[13]  P. Vandenabeele,et al.  A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death , 2012, The EMBO journal.

[14]  H. Kaufman,et al.  OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. , 2010, Future oncology.

[15]  Ken Garber,et al.  China approves world's first oncolytic virus therapy for cancer treatment. , 2006, Journal of the National Cancer Institute.

[16]  J. Almeida,et al.  The effect of trypsin on the growth of rotavirus. , 1978, The Journal of general virology.

[17]  R. Chanock,et al.  Comparison of human and animal rotavirus strains by gel electrophoresis of viral RNA. , 1978, Virology.