Particular CD81 T cells for peptides svn57 and svn82 have been detected in mice that have been initially vaccinated using the full length survivin protein, which signifies the immunodominance of those two peptides in vivo. Scientific studies uti lizing peptide exact CTL showed lytic action against GL261 cells in cytotoxicity assays. We’re actively developing these peptide vaccines and characterizing their efficacy in mouse brain tumor versions. The results of this examine could support from the advancement of a clinical trial of survivin peptide loaded DC vaccines in glioma sufferers. IM 04. TOPOTECAN INDUCES FAS ON GLIOMAS AND ENHANCES IMMUNOLOGICAL CLEARANCE Guillermo R. DeAngulo,1 Hernan Vasquez,one Nadezhda V. Koshkina,one Wei Sun,two S. Farzana Hussain,2 Eugenie S. Kleinerman,one Johannes Wolff,one Raymond Sawaya,two and Amy B. Heimberger2, 1Childrens Cancer Hospital and also the 2Brain Tumor Center, Division of Neurosurgery, The University of Texas M.
D. Anderson Cancer Center, Houston, TX, USA Glioblastoma multiforme has marked cellular heterogeneity, so, mixture therapy will possible grow to be the common. Latest strides have already been manufactured in prolonging survival in GBM individuals with each chemo therapy and immunotherapy. Typical selleck view is that admin istration of chemotherapy would mitigate the efficacy of immunotherapy, however, this view may possibly be erroneous. The expression of Fas/CD95 on tumors can render them prone to CD81 cytotoxic T cell killing. The malignant glioma cell line U 87 was treated with titrated physiological doses of topotecan, temozolomide, gemcitabine, and cisplatin as time passes to determine expression of Fas with movement evaluation cytometry. Topotecan demonstrated a 65% grow of FAS expression, as did cisplatin to a lesser degree, in contrast to temozolomide and gemcitabine.
Administration of soluble Fas ligand in MTT cell proliferation assays demonstrated a synergistic impact on U 87 cell death when pretreated with topotecan but not with temozolomide. Moreover, pretreat ment of U 87 with topotecan resulted in enhanced U 87 cell eradication by human cytotoxic CD81 T cells even at effector to target ratios of one,one inside 24 selleck chemical hours. Research are now underway to validate these findings inside a syn geneic murine model of established intracerebral tumor by up regulating Fas to the intracerebral tumor followed by immunotherapy to find out if this method could possibly be applicable to human patients. The combination of Fas upregulation,

potentially with chemotherapy, and clonal expansion of cytotoxic CD81 T cells secondary to immunotherapy might grow immune clearance, consequently maximizing the chemotherapeutic result and representing a potential synergistic method.