Ilan Y, Gabay E, Amit G, Feder R, Galun E, Adler R, Shouval D
Division of Medicine, Hadassah University Hospital, Jerusalem, Israel.
J Hepatol. 1997 Jul;27(1):170-5. doi: 10.1016/s0168-8278(97)80298-x.
BACKGROUND/AIMS: 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.
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.
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.
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.
背景/目的：先前已证明，通过将针对乙型肝炎表面抗原（HBsAg）免疫的供体的骨髓细胞移植到未免疫的受体中，可在小鼠和人类中发生针对HBsAg的免疫过继转移。在本研究中，我们评估了针对HBsAg的免疫过继转移对无胸腺小鼠中分泌HBsAg的肝细胞癌（HCC）异种移植物生长的影响。
用重组HBsAg免疫具有免疫活性的小鼠。将来自抗HBs+小鼠的骨髓细胞静脉注射到先前已皮下移植Hep3B人肝癌细胞的经照射的无胸腺Balb/c小鼠中。治疗组包括接受来自乙肝免疫（抗HBs阳性）和未免疫（抗HBs阴性）供体的骨髓移植的小鼠。
骨髓移植后9周，接受乙肝免疫骨髓细胞的无胸腺小鼠的肿瘤体积和血清甲胎蛋白水平分别为11.5立方毫米和363纳克/毫升，而未免疫骨髓移植受体的肿瘤体积和血清甲胎蛋白水平分别为1579立方毫米和19000纳克/毫升（p<0.005）。移植前对抗HBs+免疫骨髓进行T细胞清除可降低抗肿瘤作用，但并未消除该作用。在移植了不表达HBsAg的人肝癌细胞的小鼠中观察到轻度的非特异性骨髓源性移植物抗肿瘤作用。
针对乙肝的免疫过继转移有助于抑制表达HBsAg的实验性人类HCC。这种作用是特异性抗病毒表面抗原作用和非特异性移植物抗肿瘤作用共同作用的结果。
