Feasibility study of adoptive cell therapy induced by oncolytic virus for the treatment of bone tumors
Objective To explore the feasibility of oncolytic virus-induced adoptive cell therapy for the treatment of bone tumors.Methods 45 adult healthy male rats were selected to establish bone tumor model.After randomization,normal saline(control group)and oncolytic virus-induced adoptive cells(VVDD-CCL5,VVDD-CxC11,VVDD-IL15Rα,VVDD-IL2)were respectively administered,and the group with the best anti-tumor im-mune response was selected as the study object.The survival period of rats in control group and VVDD intervention group was compared,and the expressions of CD3+,CD4+,CD8+,CTLA-4,TIM-3,PD-1highTIM-3+,Foxp3+CD4+,initial T cells,TCM,TEM,4-1BB were compared in different groups.The expression of IFN-y and 4-1BB in differ-ent cells under VVDD intervention was detected in vitro.Results After 10 days of intervention,VVDD-IL-2 treated tumors showed a higher frequency of tumor reactivity CD8+TILs,and the expression of IFN-γ positive spots in VVDD-IL-2 group was higher than that in other groups(P＜0.05).The expression and survival time of CD3+,CD4+and CD8+cells in VVDD-IL 2 group were higher than those in control group(P＜0.05).The expressions of CTLA-4 and TIM-3 in VVDD-IL 2 group were higher than those in control group,while the expressions of PD-1highTIM-3+and Foxp3+CD4+in VVDD-IL 2 group were lower than those in control group(P＜0.05).The expression of TCM,TEM and 4-1BB in VVDD-IL 2 group was higher than that in control group,and the initial T cell expression was lower than that in control group(P＜0.05).The results of in vitro experiment showed that the expressions of IFN-γ and 4-1BB in tumor cells after VVDD-IL 2 intervention were higher than those without intervention(P＜0.05),and there was no statistical significance between the two groups in normal cells(P＞0.05).Conclusion Adoptive cell therapy induced by oncolytic virus can prolong the survival time of rats in the treatment of bone tumor.Il2-armed oncolytic vi-rus can promote T cell invasion and increase the number of tumor-reactive TILS.Promoting the formation and infiltra-tion of tumor-reactive TILS in low or low immunogenic tumors and expanding such TILS for cellular adoptive therapy may be a new strategy for bone tumor treatment.
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