[Feasibility of using hepatitis B virus surface antigen as target antigen in immunogen therapy against cancer].Zhonghua Yi Xue Za Zhi. 2002 Feb 25; 82(4):253-6.ZY
To investigate the feasibility of using hepatitis B virus surface antigen (HbsAg) as a tumor-associated antigen in immunogen therapy against tumor.
(1) Dendritic cells (DCs) were extracted from bone marrow of mice and cultured. Mature DCs were transfected with adenovirus vector highly expressing HBsAg and enhanced green fluorescence protein (EGFP) (DC-HBsAg). Eight C57BL/6J mice were immunized by intravenous injection of 1 x 10(6) DC-HBsAg. Seven days after, the immunization procedure was boosted by injection of the DC-HBsAg with the same dosage once more. Another eighteen mice were divided into 3 groups, 6 in each, to be injected with DC-EGFP (DCs transfected with 1 x 10(6) adenovector expressing only EGFP), 1 x 10(6) DCs, and PBS of the same volume as controls. One week after the second injection, subcutaneous injection of 7X105 mouse melanoma cells B16 or B16-HBsAg (B16 cells expressing HBsAg) was performed to each mouse. The size of tumor was measured every 2 - 3 days. When the tumor grew to the size of 2cm or caused ulcer the tumor-carrying mice were killed. The mice in the DC-HBsAg group that showed no tumorigenesis 30 days after inoculation of B16-HBsAg were re-inoculated with 7X105 B16-HBsAg. Three normal B6 mice of the same age and sex were used as controls. (2) Other patch of mice were divided into 4 groups and injected with DC-HBsAg, DC-EGFP, HBsAg (1 ug/mouse), and PBS in the same way as mentioned above. One week after the second injection at least 5 mice in each group were inoculated with 7X105 B16-HBsAg and 2 mice in each group were killed to have their serum anti-HbsAg titers examined.
(1) Seven days after inoculation of B16-HbsAg tumor began to grow in all mice in the three control groups. Tumor was found in 5 of the 8 mice in the DC-HBsA group and the other 3 mice in this group remained free of tumor. However, the size of tumor in these 5 mice was significantly smaller than thate in other groups (P < 0.01). B16-HBsAg was re-inoculated to the three mice that showed no tumor growth 30 days after the first inoculation of B16-HBsAg. However, still no tumor could be found in them. After inoculation of wild type melanoma cell B16 tumorigenesis was seen in the two immunization groups. (2) The titer of anti-HBsAg antibody induced by DC-HBsAg was obviously lower than that induced by recombinant HBsAg vaccine. However, the size of tumor in HBsAg group was obviously smaller than that in recombinant HBsAg group.
DC-HBsAg induces HBsAg-specific antitumor effect, stronger than that induced by recombinant HBsAg vaccine although the humoral immune response elicited by DC vaccine is much weaker that that induced by recombinant HBsAg vaccine. HBsAg can be used as a target antigen in immunogen therapy for treatment of cancer.