Investigating a Novel Cellular Therapy to Prevent and Treat Acute Antibody Mediated Kidney Transplant Rejection

研究预防和治疗急性抗体介导的肾移植排斥反应的新型细胞疗法

• 批准号: 10653007
• 负责人: GINNY L BUMGARDNER
• 金额: $ 53.44万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653007
• 关键词: Acute; Adoptive Cell Transfers; Adoptive Transfer; Allograft Tolerance; Allografting; Antibodies; Antibody Formation; Antibody Therapy; Antigens; Attenuated; Autoimmunity; Automobile Driving; B-Lymphocytes; BLR1 gene; Biological Assay; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cantor; Cell Communication; Cell Therapy; Cell Transplantation; Cells; Cellular immunotherapy; Chronic; Clinical; Clinical Data; Clinical Research; Cytometry; Data; Development; Dose; Down-Regulation; FOXP3 gene; Foundations; Functional disorder; Genetic; Graft Rejection; Hepatocyte; Hepatocyte transplantation; Histopathology; Human; Humoral Immunities; Hypersensitivity; IgE; Immune; Immunosuppression; Immunosuppressive Agents; Immunotherapy; In Vitro; Incidence; Interferon Type II; Interleukin-10; Interleukin-2; Islets of Langerhans Transplantation; Isoantibodies; Kidney; Kidney Failure; Kidney Transplantation; Lymphoid; Mediating; Microsurgery; Modeling; Mus; Organ Transplantation; Pathology; Patients; Phenotype; Production; Proliferating; Publishing; Qa-1 Antigen; Regulatory T-Lymphocyte; Reporting; Research; Research Personnel; Risk; Role; Severities; Skin Transplantation; Solid; Structure of germinal center of lymph node; T-Cell Depletion; T-Lymphocyte Subsets; Testing; Tissues; Transplant Recipients; Transplantation; Transplantation Immunology; Tumor Immunity; Virus Diseases; antibody-mediated rejection; autoreactivity; cancer vaccination; cytotoxic; donor-specific antibody; efficacy testing; imaging approach; immunoregulation; improved; in vivo; innovation; interleukin-21; isoimmunity; kidney allograft; liver allograft; mouse model; novel; pathogen; perforin; peripheral blood; post-transplant; pre-clinical; preclinical study; preservation; prevent; programmed cell death protein 1; prospective; response; targeted agent; trafficking; transplant model; treatment choice; vaccination strategy

Project Summary Transplant specific antibodies (alloantibodies) are known to mediate acute antibody-mediated rejection (AMR) after kidney transplant and also negatively impact long-term kidney allograft survival. Our group discovered a novel regulatory CD8+ T cell subset which suppresses alloantibody production posttransplant. We refer to these antibody suppressor CD8+ T cells as CD8+ TAb-supp cells and have developed a strategy to enhance their in vivo development, distinguish their phenotype from other alloprimed CD8+ T cells and assess their in vitro and in vivo function. In Aim 1 we will perform pre-clinical studies to investigate the efficacy of CD8+ TAb-supp cells to prevent the development of de novo post-transplant alloantibody and AMR after kidney transplant using a murine model of kidney transplant which reproduces the histopathology of AMR observed in human kidney transplant recipients. In Aim 2 we will perform pre-clinical studies to investigate the efficacy of adoptive cellular therapy with CD8+ TAb-supp cells to treat AMR and prolong kidney transplant function and survival. Our research team assembles investigators with expertise in clinical transplantation, transplant immunology, microsurgery and kidney histopathology.

项目总结