The prognosis for primary malignant brain remains poor. In a Phase I trail, one specific type of effector cell, alloreactive cytotoxic T lymphocytes (CTL), have shown promise. It is important to understand how brain tumor cells acquire resistance to immune effector cells, such as alloreactive CTL. We hypothesize that models of immunotherapy resistant tumor will display stability of resistance as determine d by cytotoxicity assays. We hypothesize that immunoresistant populations will be less susceptible to cell death and will have an increased proliferative capacity relative to parental populations. Proliferation assays combined with the TUNEL assay and standard morphologic analysis will be used to compare immunoresistant and parental populations. Cytogenetic and gene expression profiles will help identify genes, proteins and chromosomal abnormalities that may provide brain tumor cells with immunity towards alloreactive CTL selective pressure.
| Gomez, German G; Kruse, Carol A (2007) Cellular and functional characterization of immunoresistant human glioma cell clones selected with alloreactive cytotoxic T lymphocytes reveals their up-regulated synthesis of biologically active TGF-beta. J Immunother 30:261-73 |
| Zhang, Jian Gang; Eguchi, Junichi; Kruse, Carol A et al. (2007) Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. Clin Cancer Res 13:566-75 |
| Gomez, German G; Varella-Garcia, Marileila; Kruse, Carol A (2006) Isolation of immunoresistant human glioma cell clones after selection with alloreactive cytotoxic T lymphocytes: cytogenetic and molecular cytogenetic characterization. Cancer Genet Cytogenet 165:121-34 |
| Read, Susana B; Kulprathipanja, Nisha V; Gomez, German G et al. (2003) Human alloreactive CTL interactions with gliomas and with those having upregulated HLA expression from exogenous IFN-gamma or IFN-gamma gene modification. J Interferon Cytokine Res 23:379-93 |
