The immune system functions to recognize foreign antigens and develop a T-cell-based and/or antibody-based response to eliminate antigens. Cancers do not induce an immune response because they develop without eliciting any inflammation to attract an inflammatory response, express antigens that the immune system does not recognize as foreign, and because they do not have co-stimulatory molecules. Without costimulatory molecules, any T-cells that might be triggered to recognize the tumor antigen will undergo apoptosis rather than proliferate. Pre-clinical models have shown that a T-cell-based immune response can be stimulated against a tumor associated antigen when co-stimulation is present and that the immune response that develops can eliminate the tumor. Specifically, a vaccine model vaccinating against the tumor associated antigen carcinoembryonic antigen (CEA) demonstrated an increase in the CEA-specific T-cell response using a vaccine with the three costimulatory molecules, B7.1, ICAM-1 and LFA-3, compared with a vaccine with CEA alone and CEA with B7.1. This proposal seeks to test the vaccine rF-CEA (6D)/Tricom which is a recombinant fowl pox vector containing the cDNAs for CEA and the three costimulatory molecules, B7.1, ICAM-1, and LFA-3. CEA is expressed on 50 percentor more of the common adenocarcinomas, breast, lung, colon and rectum. This phase I study will examine the safety of this vaccine when given alone or in combination with granulocyte macrophage-colony stimulating factor (GM-CSF), an adjuvant known to improve the immune response. GM-CSF will be given as a recombinant protein or as a recombinant fowl pox vector encoding human GM-CSF. The immunologic response in all patients vaccinated will be assessed using intracellular cytokine assays as well as by ELISPOT assays in the HLA-A2 positive population. In addition biopsies of the vaccine site will be performed 48 hours after the vaccination to assess expression of CEA. Differences in the inflammatory infiltrate and cytokine expression at the vaccine site with and without GM-CSF will also be analyzed.
| von Mehren, Margaret (2005) Colorectal cancer vaccines: what we know and what we don't yet know. Semin Oncol 32:76-84 |
| Law, Meng; Yang, Stanley; Wang, Hao et al. (2003) Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 24:1989-98 |
