The diversity of T-cell co-stimulation in the induction of antitumor immunity.
T-cell activation has now been shown to require at least two signals. The first signal is antigen-specific, is delivered through the T-cell receptor (TCR) via the peptide/major histocompatibility complex (MHC), and causes the T cell to enter the cell cycle. The second, or co-stimulatory, signal is required for cytokine production and proliferation, and is mediated through ligand interaction on the surface of the T cell. This chapter deals with: 1) comparative studies on the use of a dual-gene construct of a recombinant vaccinia (rV) vector containing a tumor-associated antigen (TAA) gene and a co-stimulatory molecule gene vs the use of admixtures of rV-TAA and rV containing the co-stimulatory molecule to induce anti-tumor immunity; 2) the use of an admixture of vaccinia viruses containing a TAA gene and the B7-1 co-stimulatory molecule gene to induce a therapeutic response in a lung metastasis tumor model; 3) the antitumor efficacy of whole-tumor-cell vaccines in which the B7-1 co-stimulatory molecule is expressed in a tumor-cell vaccine via a vaccinia vs a retroviral vector; 4) the use of recombinant poxviruses containing the genes for the co-stimulatory molecules ICAM-1 or LFA-3 to induce antitumor immunity; and 5) the use of poxvirus vectors containing a triad of co-stimulatory molecules (B7-1, ICAM-1 and LFA-3) that synergize to enhance both CD4+ and CD8+ T-cell responses to a new threshold.
Schlom
J
J
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda MD 20892-1750, USA. js141c@nih.gov
Hodge
J W
JW
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics; D019496:Cancer Vaccines / Q000494:pharmacology; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008213:Lymphocyte Activation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000494:pharmacology; D014765:Viral Vaccines / Q000494:pharmacology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D018799:Intercellular Adhesion Molecule-1