Tl. Wang et al., Intramuscular administration of E7-transfected dendritic cells generates the most potent E7-specific anti-tumor immunity, GENE THER, 7(9), 2000, pp. 726-733
Dendritic cells (DCs) are highly efficient antigen-presenting cells capable
of priming both cytotoxic and helper T cells in vivo. Recent studies have
demonstrated the potential use of DCs that are modified to carry tumor-spec
ific antigens in cancer vaccines. However, the optimal administration route
of DC-based vaccines to generate the greatest anti-tumor effect remains to
be determined. This study is aimed at comparing the levels of immune respo
nses and anti-tumor effect generated through different administration route
s of DC-based vaccination. We chose the E7 gene product of human papillomav
irus (HPV) as the model antigen and generated a stable DC line (designated
as DC-E7) that constitutively expresses the E7 gene. Among the three differ
ent routes of DC-E7 vaccine administration in a murine model, we found that
intramuscular administration generated the greatest anti-tumor immunity co
mpared with subcutaneous and intravenous routes of administration. Furtherm
ore, intramuscular administration of DC-E7 elicited the highest levels of E
7-specific antibody and greatest numbers of E7-specific CD4(+) T helper and
CD8(+) T cell precursors. Our results indicate that the potency of DC-base
d vaccines depends on the specific route of administration and that intramu
scular administration of E7-transfected DCs generates the most potent E7-sp
ecific anti-tumor immunity.