J Immunol 1999 Jul 15;163(2):699-707
Induction of antitumor immunity with dendritic cells transduced with
adenovirus vector-encoding endogenous tumor-associated antigens.
Kaplan JM, Yu Q, Piraino ST, Pennington SE, Shankara S, Woodworth LA, Roberts BL
Genzyme Corporation, Genzyme Molecular Oncology, Framingham, MA 01701, USA. jkaplan@genzyme.com
Dendritic cells (DCs) are professional Ag-presenting cells that are being considered as potential immunotherapeutic agents to
promote host immune responses against tumor Ags. In this study, recombinant adenovirus (Ad) vectors encoding
melanoma-associated Ags were used to transduce murine DCs, which were then tested for their ability to activate CTL and
induce protective immunity against B16 melanoma tumor cells. Immunization of C57BL/6 mice with DCs transduced with Ad
vector encoding the hugp100 melanoma Ag (Ad2/hugp100) elicited the development of gp100-specific CTLs capable of lysing
syngeneic fibroblasts transduced with Ad2/hugp100, as well as B16 cells expressing endogenous murine gp100. The induction
of gp100-specific CTLs was associated with long term protection against lethal s.c. challenge with B16 cells. It was also
possible to induce effective immunity against a murine melanoma self Ag, tyrosinase-related protein-2, using DCs transduced
with Ad vector encoding the Ag. The level of antitumor protection achieved was dependent on the dose of DCs and required
CD4+ T cell activity. Importantly, immunization with Ad vector-transduced DCs was not impaired in mice that had been
preimmunized against Ad to mimic the immune status of the general human population. Finally, DC-based immunization also
afforded partial protection against established B16 tumor cells, and the inhibition of tumor growth was improved by
simultaneous immunization against two melanoma-associated Ags as opposed to either one alone. Taken together, these results
support the concept of cancer immunotherapy using DCs transduced with Ad vectors encoding tumor-associated Ags. |
