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Development of the vaccinotherapy with HDAC inhibitor regulating immunoescape

HDAC抑制剂调节免疫逃逸的疫苗疗法的开发

基本信息

批准号：
22659235
负责人：
HIRATA Kouichi
金额：
$ 2.05万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Exploratory Research
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659235/
关键词：
癌ワクチン腫瘍免疫ペプチド HDAC 癌治療

项目摘要

Cancer vaccine therapy utilizing surviving 2B peptide had been indicated for the patients with unresectable advanced or recurrent cancers during recent two years between 2010 April and 2012 March. Totally, eight patients with gastrointestinal or mammary cancers had been registered and treated under the strict maintenance by the clinical research protocol. No revere adverse effect had been experienced, but slight fever(grade II) was observed in two patients and typical skin reactions just on/in the dermal injection sites of peptide was mostly yielded but no severe allergic reaction and no ulcer formation was noted. Therefore, clinical trials by the protocol had been established. Immunological response was clearly admitted in most of patients. Clinical effect was SD in six patients and PD in two patients.The low or negative expression of MHC class I in cancer cell wall indicated no immunological effect for those cells, as one of escape mechanisms. The HDAC inhibitors have the promotion effect on the expression of MHC class I, then HDAC inhibitor pretreatment before vaccine administration was tried. The patients with the indications were registered at the end of this protocol schedule, then now is ongoing as the phase I and II. Grade I adverse effects(nausea and elevation of hepatic transaminase) were noticed but it was possible to continue under this protocol.Further investigation would be established within one year.

在2010年4月至2012年3月的近两年中，利用存活2B肽的癌症疫苗治疗已被用于不可切除的晚期或复发性癌症患者。在临床研究方案的严格维护下，共登记和治疗了8例胃肠道或乳腺癌患者。未发生严重不良反应，但在2例患者中观察到轻度发热（II级），大多数仅在肽的皮肤注射部位产生典型的皮肤反应，但未观察到重度过敏反应和溃疡形成。因此，已按照方案建立了临床试验。多数患者免疫应答明显。6例患者的临床效果为SD，2例患者为PD。癌细胞壁中MHC I类分子的低表达或阴性表达表明这些细胞没有免疫效应，这是逃逸机制之一。HDAC抑制剂对MHC I类分子的表达有促进作用，因此在疫苗接种前尝试HDAC抑制剂预处理。适应症患者在本方案时间表结束时登记，然后作为I期和II期正在进行。观察到I级不良反应（恶心和肝转氨酶升高），但仍有可能在本方案下继续进行，将在一年内进行进一步研究。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Targeting survivin in cancer therapy : Clinical considerations. Apoptosome An up-and-coming_therapeutical tool.

癌症治疗中针对生存素：临床考虑。

DOI：
发表时间：
2010
期刊：
影响因子：
0
作者：
Tsuruma. T;et al.
通讯作者：
et al.

Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses

新型寡甘露糖脂质体-DNA 复合物 DNA 疫苗接种可有效引发抗 HPV E6 和 E7 CTL 反应

DOI：
发表时间：
2012
期刊：
Exp Mol Pathol
影响因子：
3.6
作者：
Mizuuchi M;Hirohashi Y;Torigoe T;Takafumi K;Yasuda K;Saito T;Sato N.
通讯作者：
Sato N.

Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma

抗缺氧诱导因子脯氨酰羟化酶 3 的自身抗体是肾细胞癌的潜在血清学标志物

DOI：
10.1007/s00432-010-0940-6
发表时间：
2011
期刊：
J. Cancer Res. Clin. Oncol
影响因子：
0
作者：
Tanaka;T.;Kitamura;H.;Torigoe;T.;Hirohashi;Y.;Masumori;N.;Sato;N. and Tsukamoto;T.
通讯作者：
T.

HSP-癌ペプチド複合体ワクチンの高CTL誘導性機構の解析と治療への応用

HSP-癌肽结合疫苗诱导高CTL的机制分析及其治疗应用