title: Glioma big potassium channel expression in human cancers and possible T cell epitopes for their immunotherapy.
abstract: Big potassium (BK) ion channels have several spliced variants. One spliced variant initially described within human glioma cells is the glioma BK (gBK) channel. This isoform consists of 34 aa inserted into the intracellular region of the basic BK ion channel. PCR primers specific for this inserted region confirmed that human glioma cell lines and freshly resected surgical tissues from glioblastoma multiforme patients strongly expressed gBK mRNA. Normal human brain tissue very weakly expressed this transcript. An Ab specific for this gBK isoform confirmed that human glioma cells displayed this protein in the cell membrane, mitochondria, Golgi, and endoplasmic reticulum. Within the gBK region, two putative epitopes (gBK1 and gBK2) are predicted to bind to the HLA-A*0201 molecule. HLA-A*0201-restricted human CTLs were generated in vitro using gBK peptide-pulsed dendritic cells. Both gBK1 and gBK2 peptide-specific CTLs killed HLA-A2⁺/gBK⁺ gliomas, but they failed to kill non-HLA-A2-expressing but gBK⁺ target cells in cytolytic assays. T2 cells loaded with exogenous gBK peptides, but not with the influenza M1 control peptide, were only killed by their respective CTLs. The gBK-specific CTLs also killed a variety of other HLA-A*0201⁺ cancer cells that possess gBK, as well as HLA-A2⁺ HEK cells transfected with the gBK gene. Of clinical relevance, we found that T cells derived from glioblastoma multiforme patients that were sensitized to the gBK peptide could also kill target cells expressing gBK. This study shows that peptides derived from cancer-associated ion channels maybe useful targets for T cell-mediated immunotherapy.
authors: Diagnostic and Molecular Health Care Group, Long Beach, CA 90822, USA.
authors: Lisheng
authors: L
authors: Ge
authors: Neil T
authors: NT
authors: Hoa
authors: Andrew N
authors: AN
authors: Cornforth
authors: Daniela A
authors: DA
authors: Bota
authors: Anthony
authors: A
authors: Mai
authors: Dong In
authors: DI
authors: Kim
authors: Shiun-Kwei
authors: SK
authors: Chiou
authors: Michelle J
authors: MJ
authors: Hickey
authors: Carol A
authors: CA
authors: Kruse
authors: Martin R
authors: MR
authors: Jadus
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use*; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005910:Glioma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D056945:Hep G2 Cells; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D018984:Epitopes, T-Lymphocyte; D051036:Large-Conductance Calcium-Activated Potassium Channels