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01-12-2016 | Original Article

Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma

Authors: Yasuharu Akasaki, Tetsuro Kikuchi, Sadamu Homma, Shigeo Koido, Toshifumi Ohkusa, Tetsunori Tasaki, Kazumi Hayashi, Hideo Komita, Nobuyuki Watanabe, Yuta Suzuki, Yohei Yamamoto, Ryosuke Mori, Takao Arai, Toshihide Tanaka, Tatsuhiro Joki, Takaaki Yanagisawa, Yuichi Murayama

Published in: Cancer Immunology, Immunotherapy | Issue 12/2016

Abstract

Background

This trial was designed to evaluate the safety and clinical responses to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with fusions of DCs and glioma cells in patients with glioblastoma (GBM).

Method

GBM patients were assigned to two groups: a group of recurrent GBMs after failing TMZ-chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region. Toxicity, progression-free survival (PFS), and overall survival (OS) of this trial were evaluated. Expressions of WT-1, gp-100, and MAGE-A3, recognized as chemoresistance-associated peptides (CAP), were confirmed by immunohistochemistry of paraffin-embedded tumor samples. Patient’s PBMCs of pre- and post-vaccination were evaluated by tetramer and ELISPOT assays.

Results

FC-immunotherapy was well tolerated in all patients. Medians of PFS and OS of Group-R (n = 10) were 10.3 and 18.0 months, and those of Group-N (n = 22) were 18.3 and 30.5 months, respectively. Up-regulation and/or cytoplasmic accumulation of CAPs was observed in the recurrent tumors of Group-R patients compared with their initially excised tumors. Specific immune responses against CAPs were observed in the tetramer and ELISPOT assays.

Conclusions

The combination of TMZ-treatment leading to up-regulation and/or cytoplasmic accumulation of CAPs, with FC-immunotherapy as a means of producing specific immunity against CAPs, may safely induce anti-tumor effects in patients with GBM.

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Title: Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma
Authors: Yasuharu Akasaki
Tetsuro Kikuchi
Sadamu Homma
Shigeo Koido
Toshifumi Ohkusa
Tetsunori Tasaki
Kazumi Hayashi
Hideo Komita
Nobuyuki Watanabe
Yuta Suzuki
Yohei Yamamoto
Ryosuke Mori
Takao Arai
Toshihide Tanaka
Tatsuhiro Joki
Takaaki Yanagisawa
Yuichi Murayama
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 12/2016
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1905-7

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Abstract

Background

Method

Results

Conclusions

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