Abstract
tal HCCs (Hepa 1-6 cells in C57L/J mice). However, tumor vaccination strategies might be limited by low levels of tumor infiltration by effector Tlymphocytes. In the present study we therefore analyzed, if intatumoral cytokine/chemokine expression may enhance the efficiency of mAFP-specific DNA-vaccination in a highly aggressive primary murine HCC model. Materials and Methods: Subcutaneous HCC tumors expressing AFP (BW7756) were generated in C57L/J mice by transplantation of tumor pieces. DNA-vaccination was performed at days 4 and 18 by intramuscular injection of expression vectors encoding mAFP, mIL-12 and mGM-CSF. 9 days after DNA-vaccination tumors were injected with adenoviral vectors expressing mIL-12 (Ad-IL-12) and IP-10 (Ad IP-10) or b-galactosidase (Ad-b-gal) as control. Results and Discussion: DNA-vaccination alone, tumor injections with Ad-b-gal and the combination of DNA-vaccination with Ad-b-gal did not show therapeutic efficiency in mice bearing aggressive BW7756 HCCs. Intratumoral adenoviral mIL-12+IP-10 expression resulted in partial tumor regressions, but did not significantly improve animal survival. In contrast, combination of AFP-specific DNA-vaccination with intratumoral Ad-IL12 and Ad IP-10 injection resulted in tumor regressions in all treated animals and prolonged animal survival. These results demonstrate for the first time, that combination of DNA-vaccination with intratumoral gene therapeutic expression of cytokines and chemokines results in improved therapeutic efficiency. This synergistic effect might be caused by enhanced infiltration of the tumor tissue with effector lymphocytes generated by the DNA-vaccination. 90 HEPATOCYTE GP130/STAT ACTIVATION RESULTS IN LIVER PROTECTION IN IMMUNE MEDI-ATED HEPATITIS
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call