Clinical immunologic monitoring is a critical component of each of the clinical trials proposed among each of the projects of this program and constitutes the key endpoint of the clinical trials. The main function of the clinical immunologic monitoring core (Core C) will be to quantitate the CEA-specific T cell response of each of the clinical trials of this program. A secondary function of this core will be to explore new methods to quantify and quantitate antigen specific T cell responses. Interactions with biotechnology companies will allow for development of devices and methods of T cell assessment that can be expanded for the analysis of immune responses in large scale clinical trials.
The specific aims of Core C are:
Aim 1 Perform the in vitro analysis of functional CEA-specific T cell responses in peripheral blood samples from patients treated in clinical trials in projects 1 and 3 using cytotoxicity assays and ELISPOT analysis.
Aim 2 Test for the presence of CEA-specific T cells using multiparameter flow cytometric analysis of the phenotype, expression of activation marker CD69 and cytokine secretion.
Aim 3 Conduct fine specificity analysis of the structural T cell receptor (TCR) variable (V) gene and complementary determining region 3 (CDR3) of CEA-specific T cells.
Aim 4 Perform the in vitro functional analysis of T cells isolated from sites of CEA-specific DTH testing sites in patients treated with CEA RNA transfected DC.
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