Suppression of human hepatoma in mice through adoptive transfer of immunity to the hepatitis B surface antigen.
OBJECTIVE
Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) has previously been shown to occur in mice and humans through transplantation of bone marrow cells from donors immunized against HBsAg (anti-HBs) to non-immune recipients. In the present study we evaluated the effect of adoptive transfer of immunity to HBsAg on the growth of HbsAg-secreting hepatocellular carcinoma (HCC) xenografts in athymic mice.


METHODS
Immunocompetent mice were immunized with recombinant HBsAg. Bone marrow cells from anti-HBs+ mice were injected intravenously to irradiated athymic Balb/c mice which had been previously transplanted subcutaneously with Hep3B human hepatoma cells. Treatment groups included mice receiving bone marrow transplantation from HBV-immunized (anti-HBs positive) and non-immunized (anti-HBs negative) donors.


RESULTS
At 9 weeks post bone marrow transplantation, tumor volume and serum alpha-fetoprotein levels in athymic mice receiving HBV-immune bone marrow cells were 11.5 mm3 and 363 ng/ml, respectively, as compared to 1579 mm3 and 19,000 ng/ml, in recipients of non-immune bone marrow transplantation (p<0.005). T-cell depletion of antiHBs+ immune bone marrow prior to transplantation decreased the anti-tumor effect but did not abolish it. A mild nonspecific, bone marrow-derived, graft versus tumor effect was observed in mice transplanted with human hepatoma cells that do not express HBsAg.


CONCLUSIONS
Adoptive transfer of immunity to HBV facilitates suppression of experimental human HCC expressing HBsAg. This effect is the result of a combination of specific anti-viral surface antigen effect and a nonspecific graft versus tumor effect.
Ilan
Y
Y
Division of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Gabay
E
E
Amit
G
G
Feder
R
R
Galun
E
E
Adler
R
R
Shouval
D
D
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006509:Hepatitis B / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous; D000509:alpha-Fetoproteins / Q000032:analysis
D006514:Hepatitis B Surface Antigens; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins