Development of Novel Cancer Immunotherapy Targeting Mutated Genes: Identification of Antigen Epitopes Derived from the Mutated KRAS and EGFR Genes.

针对突变基因的新型癌症免疫疗法的开发：从突变的 KRAS 和 EGFR 基因衍生的抗原表位的鉴定。

• 批准号: 23591913
• 负责人: SASADA Tetsuro
• 金额: $ 3.33万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591913/
• 关键词: 免疫療法; 突然変異遺伝子; T細胞エピトープ; ペプチドワクチン; 上皮成長因子受容体（EGFR); KRAS; 上皮成長因子受容体（EGFR）; Ｔ細胞エピトープ

Personalized cancer treatments targeting oncogenic mutated genes are currently developing. Since mutated genes are recognized as foreign by the host immune system, they might be an appropriate target for cancer immunotherapy. In the current study, we have identified two antigen epitopes derived from the epidermal growth factor receptor (EGFR) T790M mutation, which is known to cause resistance to gefitinib in non-small cell lung cancer, and one antigen epitope derived from the KRAS (G12V) mutation, which is frequently detected in colorectal cancer. Our results could provide a novel immunotherapeutic approach for treatment against refractory advanced cancer patients with these mutations, and might lead to development of "personalized immunotherapy targeting mutated genes".

针对致癌突变基因的个体化癌症治疗目前正在发展中。由于突变基因被宿主免疫系统识别为外来基因，它们可能是癌症免疫治疗的合适靶点。在目前的研究中，我们已经鉴定了两个来自表皮生长因子受体（EGFR） T790M突变的抗原表位，这种突变已知会导致非小细胞肺癌对吉非替尼的耐药，以及一个来自KRAS （G12V）突变的抗原表位，这种突变在结直肠癌中经常检测到。我们的研究结果可能为治疗具有这些突变的难治性晚期癌症患者提供一种新的免疫治疗方法，并可能导致“针对突变基因的个性化免疫治疗”的发展。

项目成果

Predictive Biomarker in Cancer Patients Receiving Personalized Peptide Vaccination.

接受个性化肽疫苗接种的癌症患者的预测生物标志物。

• 发表时间: 2011
• 作者: Sasada T;Matsueda S;Shichijo S;Komatsu N;Noguchi M;Yamada A;Itoh K.
• 通讯作者: Itoh K.

EGFR T790M mutation as a possible target for immunotherapy; identification of HLA-A*0201-restricted T cell epitopes derived from the EGFR T790M mutation.

• DOI: 10.1371/journal.pone.0078389
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Yamada T;Azuma K;Muta E;Kim J;Sugawara S;Zhang GL;Matsueda S;Kasama-Kawaguchi Y;Yamashita Y;Yamashita T;Nishio K;Itoh K;Hoshino T;Sasada T
• 通讯作者: Sasada T

テーラーメイドがんペプチドワクチン療法

量身定制的癌症肽疫苗疗法

• 发表时间: 2012
• 期刊: G.I.Research
• 作者: 元井紀子;石川雄一;山田亮
• 通讯作者: 山田亮

Humoral immune responses to EGFR-derived peptides predict progression-free and overall survival of non-small cell lung cancer patients receiving gefitinib.

• DOI: 10.1371/journal.pone.0086667
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Azuma K;Komatsu N;Hattori S;Matsueda S;Kawahara A;Sasada T;Itoh K;Hoshino T
• 通讯作者: Hoshino T

Identification of Predictive Biomarkers in Cancer Patients Receiving Personalized Peptide Vaccination

接受个性化肽疫苗接种的癌症患者中预测生物标志物的鉴定

• 发表时间: 2011
• 作者: Yuichiro Hagiya;Yoshio Endo;Yutaka Yonemura;Kiwamu Takahashi;Masahiro Ishizuka;Fuminori Abe;Motowo Nakajima;Toshihisa Ishikawa;Shun-ichiro Ogura;山田亮;元井紀子 他;M Noguchi;Sasada T
• 通讯作者: Sasada T