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

被引：51

作者：

Akasaki, Yasuharu ^{[1
]}

Kikuchi, Tetsuro ^{[2
]}

Homma, Sadamu ^{[2
]}

Koido, Shigeo ^{[3
]}

Ohkusa, Toshifumi ^{[3
]}

Tasaki, Tetsunori ^{[4
]}

Hayashi, Kazumi ^{[2
]}

Komita, Hideo ^{[2
]}

Watanabe, Nobuyuki ^{[1
]}

Suzuki, Yuta ^{[1
]}

Yamamoto, Yohei ^{[1
]}

Mori, Ryosuke ^{[1
]}

Arai, Takao ^{[1
]}

Tanaka, Toshihide ^{[1
]}

Joki, Tatsuhiro ^{[1
]}

Yanagisawa, Takaaki ^{[1
]}

Murayama, Yuichi ^{[1
]}

机构：

[1] Jikei Univ, Sch Med, Dept Neurosurg, Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan

[2] Jikei Univ, Sch Med, Div Oncol, Res Ctr Med Sci,Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan

[3] Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan

[4] Jikei Univ, Sch Med, Div Blood Transfus, Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2016年 / 65卷 / 12期

关键词：

Glioma; Dendritic cell; Chemoimmunotherapy; Temozolomide; Chemoresistance; MALIGNANT GLIOMA; IN-VITRO; TUMOR; INTERLEUKIN-12; VACCINATION; RESISTANCE; IMMUNITY; DECREASES; CANCER;

D O I：

10.1007/s00262-016-1905-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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). 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. 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. 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.

引用

页码：1499 / 1509

页数：11

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