Adenovirus-transduced dendritic cells stimulate cellular immunity to melanoma via a CD4(+) T cell-dependent mechanism

We previously showed that genetic immunization of C57BL/6 mice with recombi nant adenovirus encoding human TRP2 (Ad-hTRP2) was able to circumvent toler ance and induce cellular and humoral immune responses to murine TRP2 associ ated with protection against metastatic growth of B16 melanoma. In the pres ent study we compared delivery of Ad-hTRP2 with cultured dendritic cells (D C) and direct injections of Ad-hTRP2. We show that application of Ad-hTRP2 with cultured DC enhanced protective immunity to B16 melanoma cells. Most i mportantly, delivery of recombinant adenovirus with DC alters the character of the immune response resulting in preferential stimulation of strong cel lular immunity in the absence of significant humoral immunity to the encode d antigen. Adoptive transfer of lymphocytes from mice immunized with Ad-hTR P2-transduced DC confirmed that cellular components of the immune response were responsible for rejection of B16 melanoma. The protective efficacy of Ad-hTRP2-transduced DC clearly depended on the presence of CD4(+) T helper cells. Furthermore, Ad-hTRP2-transduced DC, but not direct injection of Ad- hTRP2, were effective in the presence of neutralizing anti-adenoviral antib odies. These preclinical studies demonstrate the superiority of melanoma va ccines consisting of cultured DC transduced with recombinant adenoviruses e ncoding melanoma antigens.