Chitosan-plasmid DNA nanoplexes and adenoviruses as prostate cancer vaccines

壳聚糖质粒 DNA 纳米复合物和腺病毒作为前列腺癌疫苗

• 批准号: 7568934
• 负责人: Aliasger K Salem
• 金额: $ 16.88万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7568934
• 关键词: Adenoviruses; Affect; Antibodies; Antigen Targeting; Antigens; Binding; Biological Assay; Cancer Model; Cancer Vaccines; Cell Line; Cells; Chitosan; Chromium; Complex; DNA; DNA Sequence; Deacetylation; Dose; Drug Formulations; Enzyme-Linked Immunosorbent Assay; Gene Delivery; Immune; Immune response; Immunotherapeutic agent; Immunotherapy; Injection of therapeutic agent; Malignant neoplasm of prostate; Measures; Modeling; Mus; Nitrogen; Particulate; Polymers; Prostate Cancer Vaccine; Prostate-Specific Antigen; Prostatic Neoplasms; Solutions; System; Techniques; Testing; Time; Tissues; Transfection; Tumor Immunity; Vaccines; Viral; base; cytotoxic; in vivo; inorganic phosphate; men; nanoparticle; neoplastic cell; non-viral gene delivery; plasmid DNA; polycation; tumor; zeta potential

DESCRIPTION (provided by applicant): Prostate cancer affects over 15% of all men. Prostate cancer, when metastatic, is ultimately incurable. As a result, alternative strategies including immunotherapy are being increasingly investigated. Prostate specific antigen (PSA) is an ideal target antigen for immunotherapy because it has a narrow distribution in tissues and is expressed in virtually all prostate cancers. Gene delivery techniques have the potential to stimulate potent anti-tumor immunity. To date, studies have either focused on non-viral delivery systems such as plasmid DNA-polycation complex co-acervates or viral approaches such as the use of adenoviruses encoding prostate specific antigen. Non-viral plasmid DNA sequences contain CpG motifs. CpG motifs enhance the efficacy of Ad5-PSA vaccines tumor protection. CpG ODN delivered in particulate form is significantly more potent than delivery in solution. Chitosan is a safe natural polymer that complexes with plasmid DNA (with CpG motifs) to form non-viral gene delivery nanoparticles. The objective of this application is to test the hypothesis that co-delivery of chitosan-pcDNA-PSA nanoplexes with AdPSA will enhance tumor protection in a murine model of prostate cancer. This application will test the hypothesis that co-delivery of adenoviruses encoding the prostate specific antigen (AdPSA) with chitosan-pcDNA-PSA nanoplexes will enhance tumor protection in a murine model of prostate cancer. This will be achieved by 1) optimizing chitosan-pcDNA-PSA nanoplexes/adenovirus formulations for gene delivery, 2) characterizing the antigen-specific immune response stimulated from chitosan-pcDNA-PSA nanoplexes/adenovirus formulations and 3) evaluating the combined chitosan- pcDNA-PSA nanoplex/adenovirus formulations for immunotherapeutic protection in a murine prostate cancer model.

描述（由申请人提供）：前列腺癌影响超过15%的男性。前列腺癌，当转移时，最终是不可治愈的。因此，包括免疫疗法在内的替代策略正在受到越来越多的研究。前列腺特异性抗原（PSA）是免疫治疗的理想靶抗原，因为它在组织中的分布很窄，并且几乎在所有前列腺癌中表达。基因递送技术具有刺激有效的抗肿瘤免疫的潜力。迄今为止，研究集中于非病毒递送系统如质粒DNA-聚阳离子复合物共聚集体或病毒方法如使用编码前列腺特异性抗原的腺病毒。非病毒质粒DNA序列含有CpG基序。CpG基序增强Ad 5-PSA疫苗的肿瘤保护功效。以颗粒形式递送的CpG ODN比以溶液形式递送显著更有效。壳聚糖是一种安全的天然聚合物，与质粒DNA（具有CpG基序）复合形成非病毒基因递送纳米颗粒。本申请的目的是检验壳聚糖-pcDNA-PSA纳米复合物与AdPSA的共递送将增强前列腺癌的鼠模型中的肿瘤保护的假设。本申请将测试以下假设：编码前列腺特异性抗原（AdPSA）的腺病毒与壳聚糖-pcDNA-PSA纳米复合物的共递送将增强前列腺癌的鼠模型中的肿瘤保护。这将通过以下方式实现：1）优化用于基因递送的壳聚糖-pcDNA-PSA纳米复合物/腺病毒制剂，2）表征由壳聚糖-pcDNA-PSA纳米复合物/腺病毒制剂刺激的抗原特异性免疫应答，和3）评估组合的壳聚糖-pcDNA-PSA纳米复合物/腺病毒制剂在鼠前列腺癌模型中的免疫保护。

项目成果

Chitosan coating of copper nanoparticles reduces in vitro toxicity and increases inflammation in the lung.

• DOI: 10.1088/0957-4484/24/39/395101
• 发表时间: 2013-10-04
• 期刊: Nanotechnology
• 影响因子: 3.5
• 作者: Worthington KL;Adamcakova-Dodd A;Wongrakpanich A;Mudunkotuwa IA;Mapuskar KA;Joshi VB;Allan Guymon C;Spitz DR;Grassian VH;Thorne PS;Salem AK
• 通讯作者: Salem AK

Innovative strategies for co-delivering antigens and CpG oligonucleotides.

• DOI: 10.1016/j.addr.2008.12.013
• 发表时间: 2009-03-28
• 期刊: Advanced drug delivery reviews
• 影响因子: 16.1
• 作者: Krishnamachari Y;Salem AK
• 通讯作者: Salem AK

Exploiting the tumor phenotype using biodegradable submicron carriers of chemotherapeutic drugs.

• DOI: 10.1615/critrevoncog.2014011518
• 发表时间: 2014
• 期刊: Critical reviews in oncogenesis
• 作者: Geary SM;Salem AK
• 通讯作者: Salem AK

Proposed mechanisms of action for prostate cancer vaccines.

• DOI: 10.1038/nrurol.2013.8
• 发表时间: 2013-03
• 期刊: Nature reviews. Urology

Characterization and evaluation of the efficacy of cationic complex mediated plasmid DNA delivery in human embryonic palatal mesenchyme cells.

• DOI: 10.1002/term.1873
• 发表时间: 2016-11
• 期刊: JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
• 影响因子: 3.3
• 作者: D'Mello, Sheetal;Salem, Aliasger K.;Hong, Liu;Elangovan, Satheesh
• 通讯作者: Elangovan, Satheesh