Yasuharu Akasaki1, Tetsuro Kikuchi2, Sadamu Homma2, Shigeo Koido3, Toshifumi Ohkusa3, Tetsunori Tasaki4, Kazumi Hayashi2, Hideo Komita2, Nobuyuki Watanabe5, Yuta Suzuki5, Yohei Yamamoto5, Ryosuke Mori5, Takao Arai5, Toshihide Tanaka5, Tatsuhiro Joki5, Takaaki Yanagisawa5, Yuichi Murayama5. 1. Department of Neurosurgery, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan. akasaki@jikei.ac.jp. 2. Division of Oncology, Research Center for Medical Science, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan. 3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan. 4. Division of Blood Transfusion, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan. 5. Department of Neurosurgery, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
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.
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.
Authors: Maryam Rahman; W Gregory Sawyer; Scott Lindhorst; Loic P Deleyrolle; Jeffrey K Harrison; Aida Karachi; Farhad Dastmalchi; Joseph Flores-Toro; Duane A Mitchell; Michael Lim; Mark R Gilbert; David A Reardon Journal: Neuro Oncol Date: 2020-09-29 Impact factor: 12.300
Authors: Mahmoud S Alghamri; Brandon L McClellan; Carson S Hartlage; Santiago Haase; Syed Mohd Faisal; Rohit Thalla; Ali Dabaja; Kaushik Banerjee; Stephen V Carney; Anzar A Mujeeb; Michael R Olin; James J Moon; Anna Schwendeman; Pedro R Lowenstein; Maria G Castro Journal: Front Pharmacol Date: 2021-05-18 Impact factor: 5.988
Authors: Marion Rapp; Oliver M Grauer; Marcel Kamp; Natalie Sevens; Nikola Zotz; Michael Sabel; Rüdiger V Sorg Journal: Trials Date: 2018-05-25 Impact factor: 2.279