Amplification of the lytic potential of effector/memory CD8+ cells by vector-based enhancement of ICAM-1 (CD54) in target cells: implications for intratumoral vaccine therapy

Cancer Gene Ther. 2004 Oct;11(10):665-80. doi: 10.1038/sj.cgt.7700741.


We demonstrated that enhanced expression of the costimulatory molecules CD80, CD54 and CD48 (designated rF-TRICOM) on target cells, as delivered via a recombinant fowlpox vector, results in an increased state of stimulation of CD8+ T cells, and consequent increased lysis of target cells. CTL studies in conjunction with antibody-blocking studies demonstrated that the enhanced effector activity of these CD8+ T cells is mediated mainly through CD54. Intracellular staining of CD8+ cells that interact with target cells infected with rF-TRICOM showed that they contain higher amounts of perforin and have a higher level of perforin message. Enhanced expression of costimulatory molecules (specifically CD54) on target cells using rF-TRICOM vectors also leads to the formation of stable conjugates/synapses between targets and T cells. The interaction of T cells with target cells that overexpress costimulatory molecules upon infection with rF-TRICOM leads to enhanced signaling through Lck, ZAP70, and STAT-1 in CD8+ T cells and heightened lytic activity of CD8+ cells through the formation of a greater number of immunological synapses. This, in turn, leads to enhanced signaling in T cells. Finally, studies were conducted in mice in which CEA is a self-antigen in an attempt to understand the potential clinical relevancy of intratumoral vaccine therapy. Mice were transplanted subcutaneously with CEA expressing tumors. Intratumoral (i.t.) vaccination was administered 8 days post tumor transplant. Mice vaccinated i.t. with rF-TRICOM demonstrated significantly reduced tumor growth and 40% of the mice had complete tumor regression. The antitumor effects were further improved by the addition of tumor antigen (CEA) in the vaccination by utilizing rF-CEA/TRICOM, with 80% of the mice experiencing complete tumor regression. These studies thus support the concept of intratumoral vaccination employing vectors expressing costimulatory molecules.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / therapy*
  • Animals
  • Antigens, CD / genetics
  • B7-1 Antigen / genetics
  • Blotting, Western
  • CD48 Antigen
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / therapeutic use*
  • Carcinoembryonic Antigen / immunology
  • Cell Line, Tumor
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • Fowlpox virus / genetics
  • Gene Expression / physiology
  • Genetic Vectors*
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Perforin
  • Polymerase Chain Reaction
  • Pore Forming Cytotoxic Proteins
  • Vaccines, Synthetic / therapeutic use*


  • Antigens, CD
  • B7-1 Antigen
  • CD48 Antigen
  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Cd48 protein, mouse
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Vaccines, Synthetic
  • rF-TRICOM vaccine
  • Perforin
  • Intercellular Adhesion Molecule-1