umoral vaccination in hampering the growth of trans planted Neu overe pressing salivary gland cancer cells in syngeneic, Neu tolerant BALB neuT mice. In addition, we determined whether the efficiency of vaccin ation was dependent on rV neuT doses. Mice transgenic for the rat neu oncogene are usu ally employed to evaluate the may ability of ErbB2 Neu vaccines to inhibit the progression of neu driven carcinogenesis. Our observations indicated that the efficiency of vaccin ation was dose dependent. Mice vaccinated with 108 pfu rV neuT had a mean survival time of 27 weeks while those receiving the 107 pfu and 106 pfu rV neuT doses had a mean survival time of 5. 25 and 9. 33 weeks, respectively. rV neuT vaccination at the dose of 108 pfu induced regression of transplanted tumors while that at 106 e and 107 pfu pro voked a delay in the tumor growth as compared to V wt vaccination.
The risk of developing tumors in the 106 pfu and 107 pfu rV neuT vaccinated groups was 10. 26 and 14. 05 in comparison to the 108 pfu rV neuT vaccinated group. Overall, the mean survival time of mice vaccinated with rV neuT, independently of the dose, was 14. 8 weeks while of those receiving the V wt was 2. 63 weeks. It is of note that 8 9 rV neuT vaccinated mice were tumor free si weeks after the first vaccination and remained in this status until the 30th week. Conversely, V wt vaccinated mice were sacrificed for e ceeded tumor volume or spontaneously died at the third week after the first vaccination. We previously established that immune response and antitumor activity were increased by repeated rV neuT vaccinations.
Accordingly, we performed two immuni zations. One of the potential drawbacks in the use of many recombinant vaccinia immunizations in patients is that pre e isting and or stimulated antibody and T cell response to vaccinia virus will preclude the spread of the administered vaccinia virus and thus decrease the e pression of the inserted antigen. On the other hand, it should be noted that smallpo was eradicated worldwide more than 25 years ago. thus, young people are no longer vaccinated. In addition, recombinant avi po virus, which has a limited viral replication, can be employed to boost immune response after priming with recombinant vaccinia. The e tent of tumor growth interference in vivo was as sociated with high serum levels of anti Neu antibodies, which were able to recognize p185 Neu e pressed on SALTO tumor cells.
Cilengitide 108 pfu rV neuT vaccinated mice de veloped a significantly higher titer of anti Neu antibodies than 107 and 106 pfu rV neuT vaccinated mice. Thus, the amount of produced anti Neu antibodies was coincident with the efficiency of in vivo anti tumor activity Belnacasan (VX-765) of rV neuT vaccinated mice. Individual mechanisms including ADCC, CDC, induction of apoptosis, or receptor down regulation have been implicated to elucidate the inhibitory effect of anti ErbB2 Neu anti bodies on the growth of cancer cells e pressing ErbB2 Neu. In this study, we demonstrated that