Immunization of mice with melanoma cells transfected to secrete the superantigen, staphylococcal enterotoxin A.
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.
Shrayer
D P
DP
Department of Surgery, Roger Williams Medical Center, Brown University, Providence, RI 02908, USA.
Kouttab
N
N
Hearing
V J
VJ
Wanebo
H J
HJ
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D004768:Enterotoxins / Q000627:therapeutic use*; D007114:Immunization; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013211:Staphylococcus aureus; D018089:Superantigens / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D019496:Cancer Vaccines; D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal