Antibody association with HER-2/neu–targeted vaccine enhances CD8+ T cell responses in mice through Fc-mediated activation of DCs
J. Clin. Invest. Peter S. Kim, et al. 118:1700 doi:10.1172/JCI34333 [
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Figure 1The Fc portion of the intact 7.16.4 mAb is required for enhancement of the vaccine-induced antitumor response. (
A) Binding of F(ab′)
2 fragments of 7.16.4 (dashed line) were confirmed by flow cytometry, using secondary antibodies specific for the Fc portion and λ
1, λ
2, and λ
3 light chains. Shown are the intact antibody (solid line) and control IgG (gray histogram). (
B) Antibody-mediated enhancement of the vaccine-induced antitumor response is not seen in the vaccine + F(ab′)
2 treatment group.
neu-N mice received neu-targeted vaccine (3T3 neu/GM) or control vaccine (3T3 NP/GM), followed 2 weeks later by NT2 challenge + intact 7.16.4 mAb, + 7.16.4 F(ab′)
2, + or irrelevant IgG. The intact and control antibodies were administered weekly for a total of 5 injections (100 μg of IgG per injection). F(ab′)
2 fragments were injected twice per week for a total of 10 injections [150 μg of F(ab′)
2 per injection]. Survival curves are shown (
n = 5 per group). Statistical differences in survival among data groups were assessed using the log-rank test. This experiment was repeated once. (
C) Tumor-specific CD8
+ T cell responses were not increased in the vaccine + F(ab′)
2 treatment group when compared with the vaccine plus intact antibody treatment group. CD8
+ T cells were incubated with NT2/B7-1 target cells overnight at 37°C at 5% CO
2. IFN-γ ELISPOTs were counted on the next day. Each experiment was repeated 3 times independently. *
P < 0.05 versus intact 7.16.4 mAb + neu-targeted vaccine, Mann-Whitney
U test.
