Abstract
e21573 Background: The purpose of the study was to assess the possible synergism of strains of a new rotavirus group (Reoviridae family) and PD-1 inhibitor pembrolizumab (P) on the growth of murine transplantable melanoma В16/F10. Methods: The study was performed using a strains 228 and 100 of a new group of rotaviruses (working title «group K», RVK) ( http://jbks.ru/archive/issue-10/article-6 ). RVK is a live attenuated and apathogenic strain growing on the PEKC culture (pig embryo kidney cells) with 5·109 viral particles/mL. Melanoma B16/F10 was transplanted subcutaneously (2x106 living tumor cells/mL) to 40 female mice C57/Bl6. RVK strains (0.3 ml of a virus-containing fluid) were injected intramuscularly once a week during 5 weeks before tumor transplantation and P was administrated intramuscularly (0,04 µg once a week during the life span of the mice) after formation of the visible tumor. The 1 experimental group received RVK 228+P, the 2 – RVK 100+P, the 3 – only P, the 4 group was tumor-bearing control; n was 10 in each group. Results: 1 week after melanoma transplantation tumor was visible and palpable in all the mice except those of the 1 group; 10 days after transplantation tumor size was 0.028±0.0046 cm3 in the 1 group, 0.14±0.055 in the 2 group, 0.24±0.05 in the 3 group, 0.21±0.042 in the control group. A week later these parameters were 0.6±0.24, 0.99±0.3, 1.3±0.25, и 2.1±0.3 сm3 respectively, i.e. in all the experimental groups they were decreased vs control (р < 0.05). 3 weeks after transplantation the melanoma size became equal in the 3 and 4 groups (2.0±0.38 и 2.43±0.38 сm3 respectively) while in mice of the 1 group it remained decreased (1.17±0.26 сm3; р < 0.05). 1 month after transplantation the minimal tumor size was observed in mice of the 2 group (1.9±0.6 cm3), in the 1 group it was 2.6±0.17 сm3. By this time only 1 mouse survived in control group while 5 mice survived in the 3 and 1 groups, 6 mice in the 2 group. So in both of the groups vaccinated with RVK before P tumor burden was less than in controls and in mice with only P. The life span of all the experimental groups was similar and significantly higher than in controls. Conclusions: Application of RVK strains №228 and №100 in vaccination mode enhanced the antitumor effect of PD-1 inhibitor pembrolizumab on B16/F10 growth; this defines a solid rationale for their joint use. Strain 228 demonstrates the result in early and strain 100 – in later term of tumor growth.
Published Version
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