Comparison of the antitumor efficacies of Her-2/ neu DNA vaccines inducing contrasting IgG immunity but comparable CTL activity in mice

Abstract

The relative importance of CTL and antibodies in rejecting Her-2/ neu-expressing tumors was evaluated in preventive and therapeutic models by DNA vaccination. Four human Her-2/ neu-expressing plasmids (pNeu TM, pNeu ECD, pNeu TM-gDs, and pNeu ECD-gDs) were generated encoding either the transmembrane and extracellular domains or the extracellular domain. Interestingly, these plasmids demonstrated substantial difference in inducing Her-2/ neu-specific serum IgG according to their signal sequence when injected in BALB/c mice. pNeu TM and pNeu ECD induced high serum IgG titers. pNeu TM-gDs and pNeu ECD-gDs induced low or very low serum IgG titers, respectively. As a result, mice vaccinated with not only pNeu ECD but also pNeu ECD-gDs exhibited complete eradication of a small number of tumor cells. Nevertheless, when the number of tumor cells was increased in a therapeutic model, only pNeu ECD exhibited statistically significant antitumor immunity. These studies demonstrate that strong CTL may be sufficient in tumor prevention, but the collaboration of CTL and antibody may be required in tumor therapy.