新型佐剂SWZY对弱免疫原性小鼠黑色素瘤瘤苗的免疫增强作用

Immunopotentiation of novel adjuvant SWZY on the poorly immunogenic murine melanoma vaccine

目的:评价佐剂SWZY对弱免疫原性黑色素瘤瘤苗的免疫增强作用。方法:C57BL/6小鼠分为6组,实验组分别用5种不同配方的佐剂(FCA,FCA+IL-2+GM-CSF,FIA+IL-2+GM-CSF,FIA+SWZY,FIA+SWZY+IL-2+GM-CSF)和照射灭活的小鼠黑色素瘤细胞株D5制成瘤苗免疫小鼠,对照组免疫用不加任何佐剂的灭活D5黑色素瘤细胞。末次免疫后3d各组取半数动物检测DTH反应、脾细胞的杀伤活性以及免疫小鼠血清及脾细胞培养上清中IFN-γ和IL-10的水平,剩余半数动物接种未灭活的D5黑色素瘤细胞,3周后再次检测上述各免疫学参数。结果:与对照组小鼠比较,各实验组小鼠的DTH反应及脾细胞的杀伤活性均明显升高(P<0.05),但成瘤后随着肿瘤的增大,则呈下降趋势。成瘤前各实验组小鼠血清及脾细胞培养上清中IFN-γ的水平均高于对照组小鼠(P<0.05),但IL-10的水平均低于对照组小鼠。成瘤后各实验组及对照组小鼠血清及脾细胞培养上清中IFN-γ的水平均下降,而IL-10的水平均明显上升,其中FCA瘤苗组和FIA+SWZY瘤苗组免疫小鼠的血清及脾细胞培养上清中IFN-γ的水平仍高于对照组小鼠(P<0.05),IL-10的水平仍低于对照组小鼠(P<0.05)。结论:用5种佐剂配方制成的瘤苗免疫小鼠均能诱导对弱免疫原性肿瘤的细胞免疫应答,并增强Th1型细胞免疫的应答,但随着肿瘤的形成和逐渐进展,细胞免疫应答的效应逐渐减弱。其中佐剂SWZY与FCA的作用相当,但前者的毒副作用较小,有可能成为一种新型的人用肿瘤疫苗的佐剂。

AIM： To evaluate the immunopotentiation of novel adjuvant SWZY on the cancer vaccine of poorly immunogenic melanoma. METHODS： C57BL/6 mice immunized with inactivited D5 melanoma cells were divided into 6 groups： the control without adjuvants, with FCA, FCA ＋ IL-2 ＋ GM-CSF, FIA ＋ IL-2 ＋ GM-CSF, FIA ＋ SWZY, and FIA ＋ SWZY ＋ IL-2 ＋ GM-CSF. Three days after completion of immunization, DTH response, specific killing activity of splenocytes and the level of IFN-γ and IL-10 in serum and splenocytes＇ culture supernatant were assayed in half of the mice in each group. The rest were subject to live D5 tumor cell challenge. Three weeks after tumor inoculation, the same immunological parameters were measured. RESULTS： DTH response, splenocytes＇ killing activity of all the experimental groups were markedly higher than those in the control group （ P 〈0.05 ）, but decreased as the tumor grew larger. The level of IFN-γ in serum or splenocyte culture supernatant of each experimental group was significantly higher than that of the control （ P 〈0. 05 ） before tumor formation, whereas IL-10 level was lower than that of the control （P〈0.05）. After tumor formation, the level of IFN-γ in all groups decreased while that of IL-10 increased in general, but the levels of IFN-γ and IL-10 in group FCA and FIA ＋SWZY didn＇t change very much. CONCLUSION： All kinds of adjuvants can enhance the cell-mediated immune repsonse aginst poorly immunogenic tumor to some extent.The novel adjuvant SWZY can strengthen immunoresponses similar to FCA. With few harmful side-effect, SWZY might be a promising adjuvant for cancer vaccine.