Therapeutic effects of simultaneous expression of 4-1BBL and sPD-1 on experimental murine hepatoma.
- Author:
Hui QIU
1
;
Hui ZHANG
;
Zuo-hua FENG
;
Hui GENG
;
Gui-mei ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: 4-1BB Ligand; therapeutic use; Animals; Antigens, Surface; therapeutic use; Apoptosis Regulatory Proteins; therapeutic use; Genetic Therapy; Liver Neoplasms; metabolism; therapy; Liver Neoplasms, Experimental; metabolism; therapy; Mice; Mice, Inbred BALB C; Programmed Cell Death 1 Receptor
- From: Chinese Journal of Hepatology 2006;14(7):505-509
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the possible negative regulatory elements induced by the treatment of experimental murine hepatoma with 4-1BBL, and to investigate the synergistic effects and mechanisms of 4-1BBL and soluble PD-1 (sPD-1) in tumor therapy.
METHODSMice were inoculated intramuscularly (i.m.) with 5 x 10(5) H22 tumor cells in the right hind thigh to establish the experimental hepatoma model. The mice were randomly divided into 5 groups (12 mice in each group) after inoculation. The mice of group A, B, C and D were injected with NS, plasmid pcDNA3.1, plasmid p4-1BBL and plasmid pPD-1A respectively. The mice in group E, the combinatorial treatment group, were injected with plasmid p4-1BBL and pPD-1A together. Then the anti-tumor effects, using the tumor growth rates and mice survival rates and others as parameters, were recorded. Meanwhile, the phenotype of lymphocytes and residual tumor cells in the peri-tumor tissue were analyzed.
RESULTSEither transfection with 4-1BBL gene alone or with sPD-1 alone could inhibit tumor growth to some extent, but a more significant anticancer effect was obtained in the combinatorial treatment group (group E), in which the tumors were completely inhibited in 42% of the mice, compared with 0 in the other groups. In addition, the survival rate of mice in group E was 100%, compared with 30% in group B, 65% in group C and 62% in group D. The FACS analysis results showed that the expression level of B7-H1 and B7-DC on residual tumor cells in group C (injected with p4-1BBL alone) was higher than that on cells in other groups. The amount of CD8+ T cells in the peri-tumor tissue of group E was significantly increased.
CONCLUSION4-1BBl can induce an up-regulation of negative regulatory elements and at the same time it can enhance the anti-tumor response. The combinatorial treatment with 4-1BBL and sPD-1 can produce a positive synergistic anti-tumor effect on our murine experimental hepatoma.