GENETIC IMMUNIZATION FOR THE MELANOMA ANTIGEN MART-1 MELAN-A USING RECOMBINANT ADENOVIRUS-TRANSDUCED MURINE DENDRITIC CELLS/

Dendritic cells (DCs) are professional antigen-presenting cells that p rocess and present antigenic peptides and are capable of generating po tent T-cell immunity. A murine tumor model was developed to evaluate m ethods of genetic immunization to the human MART-1/Melan-A (MART-1) me lanoma antigen, A poorly immunogenic murine fibrosarcoma line (NFSA) w as stably transfected with the MART-1 gene. This transfected tumor [NF SA(MART1)] grows progressively in C3Hf/Kam/Sed (H-2(k)) mice. partial protection against a challenge with NFSA(MART1) could be achieved with i.m. injections of a MART-1 expression plasmid or with systemic admin istration of an adenovirus vector expressing MART-1. However, superior protection was achieved when granulocyte macrophage colony-stimulatin g factor/interleukin-4-differentiated murine DCs transduced with an ad enovirus vector expressing MART-1 were used for immunization. Both par tial and complete protection could be achieved with i.v. administratio n of MART-1-engineered DCs. Splenocytes from immunized mice contained MHC class I-restricted CTLs specific for MART-1, This preclinical mode l of genetic immunization supports a therapeutic strategy for human me lanoma.