Enhancing the recognition of tumour associated antigens.
Activated CD8+ T cells (TCD8+) 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 displayed on tumour cell surfaces. Tumour cells have been genetically modified in a variety of ways in efforts to enhance the immune recognition of TAA. An alternative strategy is the expression of TAA in recombinant or synthetic form. This has been made possible by the recent cloning of TAA recognized by TCD8+. In this communication we review recent work in our own laboratory on the expression of TAA as synthetic peptide, by "naked" plasmid DNA injected intramuscularly or transdermally, and by recombinant viruses including vaccinia (rVV), fowlpox (rFV) and adenovirus (rAd). The expression of TAA in recombinant and synthetic forms allows increased control over the quantity, location, and kinetics of TAA presentation and can result in powerful, specific, anti-tumour immune responses.
Surgery Branch, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
N P
NP
Restifo
B R
BR
Minev
A S
AS
Taggarse
B J
BJ
McFarland
M
M
Wang
K R
KR
Irvine
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D007167:Immunotherapy; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; D009842:Oligopeptides; D011994:Recombinant Proteins; D007371:Interferon-gamma