Animal experiments of immunotherapy with ovarian tumor vaccine during lymphopenia induced by chemotherapy / 中华妇产科杂志

ABSTRACT

Objective To explore the mechanisms and effects of adoptive immunotherapy with ovarian cancer vaccine modified by GM-CSF gene which was used after immunologic reconstitution during lymphopenia induced by chemotherapy.Methods Lymphopenia was induced by chemotherapy with cyclophosphamide.The immune reconstituted model was built in rats.The tumor vaccine draining lymph nodes were harvested after the ovarian cancer cells NUTU-19 modified by GM-CSF gene were injected.The effector T cells (T_E) were got after being stimulated and amplified.Enzyme-linked immunosorbent assay was used to detect the level of interleukin (IL)-2 and IL-4 secreted by T_E.Intracellular cytokine staining was used to determine frequency of tumor-specific T_E.Fluorescence-activated cell sorting (FACS) was used to detect the special cytotoxicity ofT_E killing target cells.The survival period of rats bearing pre-established abdominal ovariam carcinoma after being adoptively transferred byT_E.was observed.Results Compared with those in control group,the significant higher levels IL-2[(65.7±4.0) pg/ml]and lower levels IL-4 [(277±49) pg/ml]were observed in chemotherapy-immune recunstitution-vaccine immunization group.The amount of CD_4~+ T cells secreting interferon-γ (13.0±2.1)% were also significantly increased.The rate of the special cytotoxicity of killing T cells (86.5±1.1) % was markedly improved.The survival period of rats (110±16) days was increased in chemotherapy-immune reconstitution-vaccine immunization group.Conclusions The combined immunotherapy of chemotherapy-immune reconstitution-tumor vaccine immunotherapy may increase the frequency and function of specific tumor T_E.The specific cytotoxicity is increased and the weak reaction of T_E to tumor is improved,which showed that this therapy can enhance immune reaction.