REALIZATION OF ThE THERAPEUTIC BENEFITS OF CFLA-4 BLOCKADE

Both @I@+and (@4@ T cells have demonstrated roles in antitumor Immune response in many animal tumor systems. In many human tumor systems, although abundant literature exists on the evidence of tumor antigen-specific CD8@CTh response, only limited information is available on tumor antigen-specific CD4' T-cell response. Using the MART-l/ Melan-A (MART-i) antigen system as a prototype human tumor-assod ated antigen (TAA)and dendritic cell (DC)-based MART-i antigen presentation system (Le.,DCs transduced with an adenoviral vector-based construct carrying the MART-I gene), we explored, in vitro,the feasibifity of generating both CD8@and @ T-cell responses in the same individ tial. Here, we show that autologous DCs from both HLA-A2-positive melanoma patients and normal healthy individuals that are transduced with an adenoviral vector containing the MART-i antigen are capable of inducing both MART-i-specific CD8@ and CD4@ T cells in in vitro coculture. After several rounds of stimulation, both the CD4 and CD8' T cellssynthesized IFN-ywhentheywerespecifically stimulated. The CD8@ T cells generated in such cocultures also recognized the MART l27@35peptide, AAGIGILTV, in 4-h cytotoxidty assays. These observa lions, therefore, suggest that mi-type responses can be generated, in vitro, by stimulation with DCs that are genetically modified to express a TAA. Although the outcome of this type of genetically engineered DC-based stimulation may vary from system to system, this type of in vitro antigen presentation may be very useful in more comprehensive analyses of CD4@ T-cell response to defined TAAs,and such geneticallyengineeredautolo gotis DCs might be better candidates to serve as surrogate cancer vaccines.