The goal of this proposal is to study in detail the biological properties of T cells specific for tumor-associated antigens (TAAs) that arise either de novo (Aim 1) or postvaccination (Aim 2) in patients with melanoma. Using powerful and novel tools such as peptide/MHC tetramers and 10-color FACS analysis, we will assess the expression of up to 45 surface and intracellular markers, cytokine expression, and functional status of TAA-specific T cells isolated directly from melanoma patients. We will also determine the gene expression profiles of such cells (Aim 3) to elucidate the molecular differences between functional and dysfunctional TAA-specific T cell populations. By correlating these data with the clinical state of the patient from which each population is isolated and the eventual clinical outcome, we hope to understand why TAA-specific T cells are protective in some patients but not in others. Lastly, we will dissect the factors which mediate T cell dysfunction in cancer by testing various individual and combinations of immunomodulatory agents to induce or reverse T cell dysfunction (Aim 4). Together, these data should lead to a better understanding of the biology of the T cell response to melanoma, and may lead to improvements in current cancer immunotherapy approaches.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA090809-01
Application #
6321616
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Program Officer
Xie, Heng
Project Start
2001-04-01
Project End
2006-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$260,620
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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