title: Branched multipeptide immunotherapy for glioblastoma using human leukocyte antigen-A*0201-restricted cytotoxic T-lymphocyte epitopes from ERBB2, BIRC5 and CD99.
abstract: We investigated the use of cytotoxic T-lymphocyte (CTL) epitopes in peptide immunotherapy for glioblastoma. Three peptides (ERBB2, BIRC5 and CD99) were selected based on their peptide-T2 cell binding affinities and combined in a multipeptide cocktail or a branched multipeptide synthesized with mini-polyethylene glycol spacers. Dendritic cells (DCs) pulsed with the multipeptide cocktail or branched multipeptide were compared based on their immunophenotype and cytokine secretion. FACS analysis of alpha-type 1 polarized dendritic cells (αDC1s) revealed that both groups highly expressed CD80, CD83 and CD86, indicating that both treatments efficiently generated mature αDC1s with the expected phenotype. Production of IL-12p70, IL-12p40 and IL-10 also increased upon αDC1 maturation in both groups. CTLs stimulated by either αDC1 group ("DC-CTLs") included numerous IFN-γ-secreting cells against T2 cells loaded with the corresponding multipeptides. Large numbers of IFN-γ-secreting cells were observed when human glioblastoma cell lines and primary cells were treated with multipeptide-pulsed DC-CTLs. Both multipeptide-pulsed DC-CTL groups exhibited cytotoxic activity of 40-60% against the U251 cell line and 60-80% against primary cells. Branched multipeptide from ERBB2, BIRC5 and CD99 stably bound with T2 cells, and its cytotoxicity toward target cells was similar to that of the multipeptide cocktail. Thus, branched multipeptides could be promising candidates for immunotherapeutic glioblastoma treatment.
authors.affiliation: Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.
authors.forename: Thi-Anh-Thuy
authors.initials: TA
authors.lastname: Tran
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Sook-In
authors.initials: SI
authors.lastname: Jung
authors.affiliation: Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.|Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.|Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea.
authors.forename: Wool-Youl
authors.initials: WY
authors.lastname: Jang
authors.affiliation: Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.|Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea.
authors.forename: Kyung-Sub
authors.initials: KS
authors.lastname: Moon
authors.affiliation: Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.|Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea.
authors.forename: In-Young
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.|Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Jung
authors.affiliation: Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea.|Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Jung
mesh_terms: D000071443:12E7 Antigen / Q000737:chemistry; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D005434:Flow Cytometry; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D015789:HLA-A2 Antigen / Q000737:chemistry*; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods*; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
chemical_list: D000071443:12E7 Antigen; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077022:Survivin; C107489:BIRC5 protein, human; C061828:CD99 protein, human; C435939:HLA-A*02:01 antigen; C508053:ERBB2 protein, human
keywords: dendritic cell; glioblastoma; immunotherapy; multipeptide