ENHANCING THE RECOGNITION OF TUMOR-ASSOCIATED ANTIGENS

Activated CD8+ T cells (T-CD8+) can directly recognize malignant cells because processed fragments of tumour associated antigens (TAA), 8-10 amino acids in length and complexed with MHC class I molecules, are d isplayed on tumour cell surfaces. Tumour cells have been genetically m odified is a variety of ways ill efforts to enhance the immune recogni tion of TAA. An alternative strategy is the expression of TAA in recom binant or synthetic form. This has been made possible by the recent cl oning of TAA recognized by T-CD8+. In this communication we review rec ent work in our own laboratory on the expression of TAA as synthetic p eptide, by ''naked'' plasmid DNA injected intramuscularly or transderm ally, and by recombinant viruses including vaccinia (rVV), fowlpox (rF V) and adenovirus (rAd). The expression of TAA in recombinant and synt hetic forms allows increased control over the quantity, location, and kinetics of TAA presentation and can result in powerful, Specific, ant i-tumour immune responses.