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）：前列腺癌影响所有男性的15％以上。前列腺癌（转移性）最终是无法治愈的。结果，越来越多地研究了包括免疫疗法在内的替代策略。前列腺特异性抗原（PSA）是免疫疗法的理想靶抗原，因为它在组织中分布狭窄，几乎在所有前列腺癌中表达。基因输送技术具有刺激有效的抗肿瘤免疫力的潜力。迄今为止，研究要么集中在非病毒递送系统上，例如质粒DNA聚会复合物共有凝聚力或病毒方法，例如使用编码前列腺特异性抗原的腺病毒。非病毒质粒DNA序列包含CpG基序。 CPG基序提高了AD5-PSA疫苗保护的功效。以颗粒形式传递的CpG ODN比溶液中的递送更有效。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。该应用的目的是检验以下假设：在前列腺癌的鼠模型中，壳聚糖-PCDNA-PSA纳米纳弗斯与ADPSA的共同传递将增强肿瘤保护。该应用将检验以下假设：用壳聚糖-PCDNA-PSA-PSA纳米链路lime的腺病毒的共递送将在前列腺癌模型中增强肿瘤保护。这将通过1）进行1）优化基因递送的壳聚糖-PCDNA-PSA纳米插曲/腺病毒公式，2）表征壳聚糖特异性免疫反应，该抗原特异性免疫反应受到壳聚糖-PCDNA-PCDNA-PSA Nanoplexes/adenovirus/腺病毒配方的抗原特异性免疫反应，并评估3）评估组合壳的组合体。鼠前列腺癌模型中的免疫治疗保护。

项目成果

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

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

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

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

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