Engineered Optimal Adjuvant and Antigen Release from Biodegradable Nanoparticles

从可生物降解的纳米颗粒中释放优化的佐剂和抗原

基本信息

批准号：
7586568
负责人：
Aliasger K Salem
金额：
$ 13.2万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7586568
关键词：
Adjuvant Antigen-Presenting Cells Antigens Artificial nanoparticles Binding Biological Assay CD8B1 gene Cancer Model Carcinoma Cells Chemistry Colon Carcinoma Cytosine Data Dendritic Cells Development Dose Down-Regulation Drug Formulations Endosomes Engineering Enzyme-Linked Immunosorbent Assay Excision Guanine IL6 gene Immune response Immunization Immunotherapeutic agent Immunotherapy Injection of therapeutic agent Interleukin-12 Kinetics Lymphoma Malignant neoplasm of pancreas Methodology Modeling Molecular Weight Mus Ovalbumin Patients Polymers Pre-Clinical Model Preparation Production Radiation therapy Renal carcinoma Research Reverse Transcriptase Polymerase Chain Reaction Route Scheme Site Solid Neoplasm Surface System TLR9 gene Technology Testing Therapeutic Treatment Protocols Tumor Antigens Up-Regulation Vaccines base cancer type cell type chemokine chemotherapy comparative efficacy cytokine design innovation melanoma nanoparticle novel strategies particle phosphorothioate pre-clinical programs public health relevance receptor response scale up uptake

Adjuvant Antigen-Presenting Cells Antigens Artificial nanoparticles Binding Biological Assay CD8B1 gene Cancer Model Carcinoma Cells Chemistry Colon Carcinoma Cytosine Data Dendritic Cells Development Dose Down-Regulation Drug Formulations Endosomes Engineering Enzyme-Linked Immunosorbent Assay Excision Guanine IL6 gene Immune response Immunization Immunotherapeutic agent Immunotherapy Injection of therapeutic agent Interleukin-12 Kinetics Lymphoma Malignant neoplasm of pancreas Methodology Modeling Molecular Weight Mus Ovalbumin Patients Polymers Pre-Clinical Model Preparation Production Radiation therapy Renal carcinoma Research Reverse Transcriptase Polymerase Chain Reaction Route Scheme Site Solid Neoplasm Surface System TLR9 gene Technology Testing Therapeutic Treatment Protocols Tumor Antigens Up-Regulation Vaccines base cancer type cell type chemokine chemotherapy comparative efficacy cytokine design innovation melanoma nanoparticle novel strategies particle phosphorothioate pre-clinical programs public health relevance receptor response scale up uptake

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项目摘要

DESCRIPTION (provided by applicant): Our objective is to engineer the release of adjuvant co-entrapped with tumor specific antigens for immunotherapeutic treatment of melanoma. The specific aims are: (1) Engineer biodegradable nanoparticles for enhanced immunotherapeutic responses by preparing cytosine-phosphorothiolate-guanine oligodeoxynucleotides (CpG)-antigen fusion conjugates and double layered particles with antigens covalently attached on the surface of the particles and CpG entrapped within the particle matrix. Following optimization of the particle formulation methodology, the immune response initiated by the particle vaccines will be characterized by quantifying the cytokine/chemokine production and upregulation and downregulation of Toll-like receptor 9 (TLR9), IFN-3, IL- 6 and IL-12 using RT-PCR and ELISA assays. (2) Evaluate the optimal pre-clinical vaccine strategy for immunotherapeutic treatment in a murine melanoma model by determining the dosing regimen (route of administration and number of doses) that produces maximal immune response. The optimized nanoparticle vaccine will then be tested against alternative immunotherapeutic treatments. The proposed research represents a novel approach of nanoparticle engineering to provide the optimal release kinetics of adjuvant and antigens in stimulating potent immunotherapeutic responses against carcinomas. The development of a potent immunotherapeutic vaccine against melanoma will establish a framework which can be applied to a range of other cancer models including lymphoma, renal carcinoma, colon cancer and pancreatic cancer. PUBLIC HEALTH RELEVANCE: Our objective is to engineer the release of adjuvant co-entrapped with tumor specific antigens for immunotherapeutic treatment of melanoma. The specific aims are: (1) Engineer biodegradable nanoparticles for enhanced immunotherapeutic responses by preparing cytosine-phosphorothiolate-guanine oligodeoxynucleotides (CpG)-antigen fusion conjugates and double layered particles with antigens covalently attached on the surface of the particles and CpG entrapped within the particle matrix. (2) Evaluate the optimal pre-clinical vaccine strategy for immunotherapeutic treatment in a murine melanoma model by determining the dosing regimen (route of administration and number of doses) that produces maximal immune response.

描述（由申请人提供）：我们的目的是设计与肿瘤特异性抗原合作的辅助释放，以进行黑色素瘤的免疫治疗。具体目的是：（1）通过制备可生物降解的纳米颗粒，用于通过制备细胞质 - 磷酸酪氨酸 - 瓜氨酸 - 瓜氨酸寡脱氧核苷酸（CPG）抗原融合偶联物和双层分层粒子，并与植物共同于粒子的表面和cpg的植物和CPG的抗原粒子，并在抗原上，并在抗原上构成了抗原。在优化了颗粒制剂方法之后，颗粒疫苗引发的免疫反应将以量化细胞因子/趋化因子的产生以及使用RT-PCR和ELISA分析的细胞因子/趋化因子产生以及TOLL样受体9（TLR9），IFN-3，IL-6和IL-12的上调以及下调。（2）通过确定产生最大免疫反应的剂量方案（给药途径和剂量途径和剂量），评估在鼠类黑色素瘤模型中的最佳临床前疫苗策略，以进行免疫治疗。然后将针对替代免疫治疗治疗进行优化的纳米颗粒疫苗。拟议的研究代表了纳米颗粒工程的一种新方法，以在刺激针对癌的刺激有效的免疫治疗反应中提供辅助和抗原的最佳释放动力学。针对黑色素瘤的有效免疫治疗疫苗的开发将建立一个框架，该框架可以应用于淋巴瘤，肾癌，结肠癌和胰腺癌等其他一系列癌症模型。公共卫生相关性：我们的目标是设计与肿瘤特异性抗原辅助释放以进行黑色素瘤的免疫治疗。具体目的是：（1）通过制备可生物降解的纳米颗粒，用于通过制备细胞质 - 磷酸酪氨酸 - 瓜氨酸 - 瓜氨酸寡脱氧核苷酸（CPG）抗原融合偶联物和双层分层粒子，并与植物共同于粒子的表面和cpg的植物和CPG的抗原粒子，并在抗原上，并在抗原上构成了抗原。（2）通过确定产生最大免疫反应的剂量方案（给药途径和剂量途径和剂量），评估在鼠类黑色素瘤模型中的最佳临床前疫苗策略，以进行免疫治疗。