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

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.