Shrayer D P, Kouttab N, Hearing V J, Wanebo H J
Department of Surgery, Roger Williams Medical Center, Brown University, Providence, RI 02908, USA.
Cancer Immunol Immunother. 1998 Mar;46(1):7-13. doi: 10.1007/s002620050453.
Immunization of mice with a melanoma vaccine coupled with staphylococcal enterotoxin A (SEA) inhibits the growth of primary melanoma tumors in mice. We have now successfully transfected B16 cells with the sea gene and have immunized C57BL/6 mice subcutaneously once per week for 4 weeks prior to tumor challenge with vaccines of irradiated B16 cells or, 4 weeks following tumor challenge of naive mice with B16 cells, with irradiated B16 cells transfected with the sea gene. Primary tumor growth following both types of treatments was inhibited significantly. To characterize immune responses to these immunogens, we examined the production of antibodies to the B700 melanoma antigen, the stimulation of endogenous IL-2 production, the expression of CD4, CD8, Vbeta and CD25 T cell markers, and the induction of NK activity. At 4 weeks following immunization of mice, there was a significant increase (P<0.05) in levels of interleukin-2 production by splenocytes from mice immunized with SEA-secreting B16 cells or with the parental B16 cells, compared to controls. Levels of antibodies to the B700 melanoma antigen were also significantly higher in mice immunized with the SEA-secreting B16 cells, as was expression of CD4, CD8, CD25 and Vbeta T cell antigens, particularly CD4. Natural killer cell activity (at various E:T ratios) was tenfold higher in splenocytes of mice immunized with SEA-secreting B 16 cells, and fivefold higher in mice immunized with the parental B16 cells, compared to controls. These data confirm the possibility of using irradiated murine melanoma cells transfected to secrete SEA in vaccines targeted at preventing the development and growth of melanoma.
用结合了葡萄球菌肠毒素A（SEA）的黑色素瘤疫苗免疫小鼠，可抑制小鼠原发性黑色素瘤肿瘤的生长。我们现已成功地用sea基因转染了B16细胞，并在给小鼠接种经辐照的B16细胞疫苗进行肿瘤攻击前，每周一次皮下免疫C57BL/6小鼠，共4周；或者在用B16细胞对未免疫小鼠进行肿瘤攻击4周后，用转染了sea基因的经辐照的B16细胞进行免疫。两种治疗后的原发性肿瘤生长均受到显著抑制。为了表征对这些免疫原的免疫反应，我们检测了针对B700黑色素瘤抗原的抗体产生、内源性IL-2产生的刺激、CD4、CD8、Vβ和CD25 T细胞标志物的表达以及NK活性的诱导。在小鼠免疫4周后，与对照组相比，用分泌SEA的B16细胞或亲本B16细胞免疫的小鼠脾细胞产生的白细胞介素-2水平显著升高（P<0.05）。用分泌SEA的B16细胞免疫的小鼠中，针对B700黑色素瘤抗原的抗体水平也显著更高，CD4、CD8、CD25和Vβ T细胞抗原的表达也是如此，尤其是CD4。与对照组相比，用分泌SEA的B16细胞免疫的小鼠脾细胞的自然杀伤细胞活性（在各种E:T比率下）高10倍，用亲本B16细胞免疫的小鼠高5倍。这些数据证实了在旨在预防黑色素瘤发生和生长的疫苗中使用经转染以分泌SEA的辐照鼠黑色素瘤细胞的可能性。
