Multiple Antigen-Engineered DC Immunication & IFNa Boost for Metastatic Melanoma

多抗原工程 DC 免疫

基本信息

批准号：
7408306
负责人：
Lisa Helene Butterfield
金额：
$ 13.36万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-10-01 至 2012-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7408306
关键词：
Adenovirus Vector Adenoviruses Antigen Targeting Antigens Arts Autologous Autologous Dendritic Cells Avidity Biological Assay Biology Biopsy CD4 Positive T Lymphocytes CTAG1 gene Cells Clinical Clinical Trials Correlation Studies Coupled Cross-Priming Dendritic Cell Vaccine Dendritic Cells Deposition Disease Dopachrome isomerase Dose End Point Engineering Evolution Frequencies Immune Immune response Immunity Immunization Immunologic Monitoring Interferon-alpha Interferons Interleukin-10 Interleukin-2 Interleukin-5 Laboratory Study Length Localized Lymphocyte MAGEA3 gene MART-1 Tumor Antigen Mediating Metastatic Melanoma Monophenol Monooxygenase Patients Phase II Clinical Trials Phenotype Production Randomized Range Site Staging Staining method Stains Stimulus T-Cell Activation T-Lymphocyte Testing Therapeutic Time Treatment Protocols Tumor Antigens Tumor-Infiltrating Lymphocytes Unresectable Upper arm Vaccination Vaccine Therapy Vaccines Variant Viral base cytokine design enzyme linked immunospot assay improved in vivo insight melanoma melanoma-associated antigen neoplastic cell neutralizing antibody peripheral blood response trafficking tumor

项目摘要

Project 2: Multiple Antigen-Engineered DC Immunization and IFNa Boost for Metastatic Melanoma This application will build on progress made in our previous tumor antigen targeting trials to test a new genetically engineered dendritic cell-based vaccine regimen designed to more potently activate CDS and CD4 T cells specific to multiple melanoma antigens. We will couple this vaccine trial with thorough immunological monitoring to study T cell responses to the vaccine and the importance of determinant spreading for clinical response. We hypothesize that vaccination with multiple full length tumor antigens will activate a broad range of CD4 and CDS T cells, and that in the subset of patients who further activate and diversify their T cell response to include other antigens expressed by their tumor (or undergo "determinant spreading"), objective clinical response will be observed. We also hypothesize that systemic IFNa delivered after the vaccine will boost the vaccine-specific T cell responses. A. Specific Aims: A.1. Conduct an Antigen-Engineered DC Trial with an IFNa Boost. We will treat 30 subjects with antigen engineered DC and randomize half to receive an IFNa boost. A.2.Assess the Biology of the CDS and CD4 Immune Responses to Immunizing Antigens MART-1, Tyrosinase and MAGE-A6. We will follow CDS and CD4 T cell responses to the three immunizing antigens, as well as the adenovirus vector. We will also investigate TIL responses to the immunizing antigens and tumor antigen expression in accessible tumor deposits. A.3. Assess Determinant Spreading. We will also follow the CDS and CD4 T cell responses to defined melanoma-associated antigens not included in the vaccine but commonly expressed by tumors (including gplOO) and uncharacterized antigens expressed by autologous tumor to determine the importance of determinant spreading to objective clinical response.

项目2：多种抗原工程DC免疫和IFNA促进转移性黑色素瘤该应用程序将基于我们以前的肿瘤抗原靶向试验的进展，以测试一个新的基于基于树突的基于树突状细胞的疫苗方案，旨在更有效地激活CD和 CD4 T细胞特异于多种黑色素瘤抗原。我们将把这次疫苗试验与彻底搭配免疫学监测以研究对疫苗的T细胞反应和决定因素的重要性扩散以进行临床反应。我们假设使用多个全长肿瘤抗原的疫苗接种将激活广泛的CD4和CD T细胞，并在进一步激活和的患者子集中多样化其T细胞反应以包括其他肿瘤表达的其他抗原（或经历了“决定因素” 传播”），将观察到客观的临床反应。我们还假设提供了全身性IFNA 疫苗后，疫苗会增强疫苗特异性T细胞反应。 A.具体目的： A.1。用IFNA提升进行抗原工程直流试验。我们将用抗原治疗30名受试者设计直流并随机进行一半以接收IFNA提升。 a.2.评估CD和CD4免疫反应的生物学对免疫抗原Mart-1的免疫反应，酪氨酸酶和法师A6。我们将遵循CD和CD4 T细胞对三种免疫抗原的反应，以及腺病毒载体。我们还将研究直到对免疫抗原的反应，肿瘤抗原表达在可及的肿瘤沉积物中。 A.3。评估行为扩散。我们还将遵循CD和CD4 T细胞响应定义黑色素瘤相关的抗原不包括在疫苗中，而是由肿瘤表达（包括自体肿瘤表达的Gploo）和未表征的抗原，以确定确定性扩散到客观的临床反应。