Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA078673-04
Application #
6666296
Study Section
Subcommittee G - Education (NCI)
Project Start
2002-09-30
Project End
2003-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
2002
Total Cost
$86,268
Indirect Cost

  Institution

Name
Duke University
Department
Type
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Aldhamen, Y A; Seregin, S S; Kousa, Y A et al. (2013) Improved cytotoxic T-lymphocyte immune responses to a tumor antigen by vaccines co-expressing the SLAM-associated adaptor EAT-2. Cancer Gene Ther 20:564-75
Morse, Michael A; Niedzwiecki, Donna; Marshall, John L et al. (2013) A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann Surg 258:879-86
Osada, Takuya; Morse, Michael A; Hobeika, Amy et al. (2012) Novel recombinant alphaviral and adenoviral vectors for cancer immunotherapy. Semin Oncol 39:305-10
Seregin, Sergey S; Aldhamen, Yasser A; Rastall, David P W et al. (2012) Adenovirus-based vaccination against Clostridium difficile toxin A allows for rapid humoral immunity and complete protection from toxin A lethal challenge in mice. Vaccine 30:1492-501
Ren, Xiu-Rong; Wei, Junping; Lei, Gangjun et al. (2012) Polyclonal HER2-specific antibodies induced by vaccination mediate receptor internalization and degradation in tumor cells. Breast Cancer Res 14:R89
Schuldt, Nathaniel J; Aldhamen, Yasser A; Appledorn, Daniel M et al. (2011) Vaccine platforms combining circumsporozoite protein and potent immune modulators, rEA or EAT-2, paradoxically result in opposing immune responses. PLoS One 6:e24147
Seregin, Sergey S; Aldhamen, Yasser A; Appledorn, Daniel M et al. (2011) TRIF is a critical negative regulator of TLR agonist mediated activation of dendritic cells in vivo. PLoS One 6:e22064
Osada, Takuya; Chen, Minyong; Yang, Xiao Yi et al. (2011) Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations. Cancer Res 71:4172-82
Seregin, Sergey S; Aldhamen, Yasser A; Appledorn, Daniel M et al. (2011) Use of DAF-displaying adenovirus vectors reduces induction of transgene- and vector-specific adaptive immune responses in mice. Hum Gene Ther 22:1083-94
Hartman, Zachary C; Yang, Xiao-Yi; Glass, Oliver et al. (2011) HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis. Cancer Res 71:4380-91

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