Human Cancer Immunology
The identification of melanocyte-lineage restricted antigens (such as gp100 and MART1/Melan-A) that are over-expressed in metastatic melanoma serves as the starting point for vaccine strategies to elicit tumor specific effector T cells. Recent data from our laboratory shows that melanoma specific cytotoxic T lymphocytes (CTL) can be isolated from patients that are immunized with gp100 melanoma antigen peptide-pulsed dendritic cells (DC). In a phase I clinical trial, all 12 patients had detectable circulating melanoma-peptide specific CTL after DC vaccination. Our interest is to develop additional clinical trials using DC to hyper-immunize patients with advanced melanoma. Immunological monitoring of patients is essential toward understanding the kinetics and magnitude of melanoma antigen specific CTL after immunization. Full characterization of antigen-specific CTL from immunized patients is viewed as a high priority. Tumor profiling will be done longitudinally to assess mechanisms of resistance and immune evasion. The long term goal is to create effective immunotherapies for patients with advanced melanoma.
Glioma Biomarkers
The standard treatment for human glioblastoma multiforme (grade IV astrocytoma) is surgical resection followed by radiation with concurrent temozolomide followed by adjuvant temozolomide. Despite recent advances with addition of chemotherapy, most patients develop disease progression by 12 months. In a collaborative effort with members of the Neuro-Oncology faculty, my interest is to develop new clinical trials utilizing novel biomarkers to stratify patients into treatment groups evaluating investigational therapies. The long term goal is to employ a biomarker based strategy to select optimal first line treatment for patients with glioblastoma multiforme.
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Hierarchical clustering of cDNA gene expression data in patients with newly diagnosed stage I-III breast cancer
Cases with pathological complete response are underlined.
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From: Stec J, Wang J, Coombes K, Ayers M, Hoersch S, Gold DL, Ross JS, Hess KR, Tirrell S, Linette G, Hortobagyi GN, Fraser Symmans W, Pusztai L
Comparison of the predictive accuracy of DNA array-based multigene classifiers across cDNA arrays and Affymetrix GeneChips.
J Mol Diagn 2005 Aug;7(3):357-67