Development of new diagnostic and immunotherapeutic methods for patients with cancer

为癌症患者开发新的诊断和免疫治疗方法

基本信息

批准号：
14104013
负责人：
KAWAKAMI Yutaka
金额：
$ 70.14万
依托单位：
KEIO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (S)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2006
项目状态：
已结题

项目摘要

We have established basics for development of new diagnostic and therapeutic methods for various cancers of digestive organs. 1) Identification of human tumor antigens and individualized immunotherapy : Various tumor antigens and T cell epitopes were identified by using systematic gene analysis and cDNA cloning using human IgG from immunodeficient mice implanted with human cancer tissues. The analysis of the immune responses revealed importance of individualized immunotherapy. Intratumoral administration of peptide pulsed dendritic cells was developed, and it resulted in induction of strong immune responses and anti-tumor effects through antigen spreading. 2) Immune responses to MSI^+ cancers : The immune response to tumor specific frameshift peptides was found to explain good prognosis of patients with MSI^+ cancers, indicating possible immunotherapy to MSI^+ cancers. The immune response to a cancer-testis antigen CAGE was frequently detected in the patients with MSI^+ cancers, sugges … More ting its use in the immunotherapy. 3) Mechanisms for immune escape of cancer cells : Using newly developed mutation specific viral shRNAs, enhanced MAPK signaling through the BRAF or RAS mutation was found to cause production of multiple immunosuppressive factors, indicating immunotherapy in combination with signal inhibitors. 4) Immunological implications of cancer stem cells and epithelial mescenchymal transition (EMT) : Differential expression of tumor antigens in the established stem like pancreatic cancer SP cells and EMT cells was found. EMT was found to enhance tumor metastasis through immunosuppression. 5) Clinical applications of the identified tumor antigens : IgG Abs for tumor antigens were found to be useful for prognostic diagnosis. Anti-p53 Ab was found to be useful for early diagnosis of colon cancer in the patients with ulcerative colitis. Tumor markers useful for diagnosis of high metastatic ability were identified. The identified tumor antigens and immune-interventions are expected to be evaluated in the future clinical trials. KU-CR4 is a potential target for antibody therapy. Less

我们为开发各种消化器官癌的新诊断和治疗方法建立了基础。 1）鉴定人肿瘤抗原和个性化免疫疗法：通过使用系统的基因分析和使用人类IgG植入人类癌组织的免疫缺陷小鼠中的人IgG来鉴定各种肿瘤抗原和T细胞表位。对免疫调查的分析揭示了个性化免疫疗法的重要性。开发了肿瘤内给药的肽脉冲树突状细胞，并通过抗原扩散导致强烈的免疫复杂和抗肿瘤作用诱导。 2）对MSI^+癌症的免疫反应：发现对肿瘤特异性移状的免疫响应被发现解释了MSI^+癌症患者的良好预后，表明可能对MSI^+癌症的免疫疗法。 MSI^+癌症患者经常发现对癌症抗原笼的免疫激素，这表明……更多地在免疫疗法中使用。 3）癌细胞免疫探测的机制：使用新开发的突变特异性病毒shRNA，通过BRAF或RAS突变增强的MAPK信号传导会导致多种免疫抑制因子的产生，表明与信号抑制剂结合使用免疫疗法。 4）癌症干细胞和上皮间充质转变（EMT）的免疫学意义：在已建立的茎中肿瘤抗原的差异表达（如胰腺癌SP细胞和EMT细胞）。发现EMT通过免疫抑制来增强肿瘤转移。 5）发现肿瘤抗原的临床应用：发现肿瘤抗原的IgG ABS可用于预后诊断。发现抗p53 AB可用于溃疡性结肠炎患者结肠癌的早期诊断。鉴定出可用于高转移能力诊断的肿瘤标记。预计将在未来的临床试验中评估已鉴定的肿瘤抗原和免疫干预。 KU-CR4是抗体治疗的潜在靶标。较少的