Branched multipeptide immunotherapy for glioblastoma using human leukocyte antigen-A*0201-restricted cytotoxic T-lymphocyte epitopes from ERBB2, BIRC5 and CD99
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Young-Hee Kim1, Thi-Anh-Thuy Tran1, Hyun-Ju Lee2, Sook-In Jung3, Je-Jung Lee2,4, Wool-Youl Jang1,5, Kyung-Sub Moon1,5, In-Young Kim1,5, Shin Jung1,5, Tae-Young Jung1,5
1Brain Tumor Research Laboratory, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea
2Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea
3Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
4Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam, Republic of Korea
5Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea
Tae-Young Jung, email: email@example.com
Keywords: multipeptide, immunotherapy, glioblastoma, dendritic cell
Received: October 01, 2015 Accepted: June 29, 2016 Published: July 08, 2016
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.
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