Current studies have on the identification of novel antigens expressed in melanoma and renal cancers as well as the characterization of T cells that recognize epitopes of previously described antigens. In a recent studies, several novel point-mutated genes have been identified as the targets of melanoma-reactive TIL that mediated long terms clinical tumor regression following adoptive transfer. Current investigations are being carried out to evaluate the potential role of these mutated gene products in promoting the growth or metastasis of tumor cells. Additional studies have involved the identification of T cell receptors (TCRs) directed against widely shared antigens. Recent studies have focused on the identification of TCRs that recognize cancer/testis (C/T) antigens, molecules that are expressed in melanoma as well as a variety of highly prevalent malignancies such as breast and prostate cancer. A TCR that recognizes the NY-ESO-1 C/T antigen was used to transduce autologous PBMC, and results of a Phase II clinical trial published in January of 2011 indicate that approximately 50% of either melanoma or synovial cell sarcoma patients who received transudced PBMC demonstrated objective clinical responses to adoptively transferred autologous PBMC that were transduced with the NY-ESO-1 TCR. The DNA core facility provides services to many of the members of the Surgery Branch, which includes expertise and reagents used for RT-PCR, quantatitive RT-PCR, gene cloning and RNA/DNA analysis. For some of these studies, sequences were analyzed on an Applied Biosystems 3100-Avant Genetic Analyzer that is a part of the Surgery Branch DNA Sequencing Core. The FACS Core Facility is currently being utilized for the analysis of T cell populations that are administered to patients as a part of the analysis of ongoing clinical cancer adoptive immunotherapy trials. In addition, the FACS Core is utilized on a daily basis for the analysis of the results of experiments to analyze the results of in vitro experiments to examine factors that influence the phenotype and function of tumor reactive T cells as well as to carry out the separation of cells based upon their expression of a wide variety of cell surface markers. For these studies phenotypic analyses were carried out on a BD FACSCalibur, FACSCantoI and FACSCantoII, and cell separations were carried out on a BD FACSAriaIIu.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC010948-04
Application #
8350117
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$1,753,141
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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