Immunotherapy of Adenovirus Infections in Stem Cell Transplnt Recipients

干细胞移植受体中腺病毒感染的免疫治疗

• 批准号: 7337161
• 负责人: PHYLLIS Rudolph FLOMENBERG
• 金额: $ 29.72万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7337161
• 关键词: Acute; Adenovirus Infections; Adenovirus Protein; Adenoviruses; Adult; Age; Allogenic; Antigen Presentation; Antigens; Biological Assay; CD8B1 gene; Cancer Patient; Capsid Proteins; Cells; Class; Clinical; Clinical Treatment; Clinical Trials; Cytotoxic T-Lymphocytes; Data; Dendritic Cells; Disease; Donor Lymphocyte Infusion; Epitopes; Flow Cytometry; Frequencies; Future; General Population; Goals; Histocompatibility Antigens Class II; Human Herpesvirus 4; Immune; Immune response; Immunotherapeutic agent; Immunotherapy; In Vitro; Individual; Infection; Lead; Mediating; Memory; Messenger RNA; Morbidity - disease rate; Outcome; Patients; Pattern; Peptides; Play; Proteins; Rate; Recovery; Research Personnel; Risk Factors; Role; Serotyping; Specificity; Stem cell transplant; Stem cells; T memory cell; T-Cell Depletion; T-Lymphocyte; T-Lymphocyte Epitopes; Transplant Recipients; Viral; Virus; Virus Diseases; Work; adult stem cell; base; cytokine; enzyme linked immunospot assay; graft vs host disease; improved; in vivo; mortality; peripheral blood; post-transplant disease; programs; reconstitution; response; synthetic peptide; tool

The goal of this proposal is to identify potential immunotherapeutic targets for treatment of adenovirus disease in cancer patients who receive allogeneic stem cell transplants. Although adenoviruses can cause fatal infections post- stem cell transplant, there is no established therapy. Based on the successful use of donor lymphocyte infusions to treat other viral infections such as Epstein Barr virus, we propose that T cell immunotherapy may help control adenovirus disease post-transplant. Our lab was the first to document adenovirus -specific memory CD4+ and CD8+ T cell responses in peripheral blood from most healthy adults. We have identified hexon as the immunodominant capsid protein target, containing epitopes highly conserved among different adenovirus serotypes. However, it is not known whether hexon-specific T cell responses alone are adequate to control acute infection. We hypothesize that, in vivo, T cells targeted to regulatory adenovirus proteins expressed early in infected cells may be more efficient than hexon-specific J cells because they will 1)eliminate infected cells prior to viralreplication and 2) recognize cells prior to adenovirus ¿3 19k-mediated inhibition of MHC class l-restricted antigen presentation. We propose to identify major early protein targets by analysis of memory adenovirus-specific T cell responses in healthy adults against individual proteins and synthetic peptides. Additionally, patterns of virus-specific T cell responses in stem cell transplant recipients who develop acute adenovirus infections will be evaluated by IFN-y ELISPOT, cytokine flow cytometry, and cytotoxic T cell assays and correlated with clinical outcomes. These studies will provide the tools and scientific basis for a future immunotherapy trial for the treatment of adenovirus disease. It is anticipated that this work will lead to an improvement in the survival of patients who undergo stem cell transplants.

本提案的目的是确定潜在的免疫治疗靶点