权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A lung cancer vaccine based on exosomes of induced pluripotent stem cells

基于诱导多能干细胞外泌体的肺癌疫苗

基本信息

批准号：
10651014
负责人：
Chi Li
金额：
$ 40.24万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10651014
关键词：
Adjuvant Adult Allogenic Antigen Presentation Autoimmune Responses Autoimmunity CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cancer Vaccines Carcinoembryonic Antigen Categories Cells Chimera organism Clinical Trials Coculture Techniques Enterobacteria phage P1 Cre recombinase Exclusion Fibroblasts Frequencies Germ Cells Goals Grant Granulocyte-Macrophage Colony-Stimulating Factor Human Immune response Immunity Immunocompetent Immunotherapeutic agent Implant In Vitro Individual Lung Lung Adenocarcinoma Lung Neoplasms Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Measures Mediating Modeling Monoclonal Antibodies Mus Operative Surgical Procedures Patients Pluripotent Stem Cells Prevention approach Probability Property Recurrence Residual Neoplasm Resistance Serum Somatic Cell Source Splenocyte Subgroup T cell response T-Cell Depletion TP53 gene Testing Tissues Tumor Antigens Tumor Immunity Tumor-Infiltrating Lymphocytes Tumorigenicity Vaccinated Vaccination Vaccines anti-cancer anticancer research antitumor effect cell type clinically relevant conventional therapy cytotoxic cytotoxic CD8 T cells early embryonic stage effectiveness evaluation effector T cell embryonic stem cell exosome experimental study immunogenic improved in vivo induced pluripotent stem cell innovation loss of function lung development lung tumorigenesis mouse model mutant neoplastic cell prevent response self-renewal success translational potential tumor tumor eradication tumor initiation tumorigenesis tumorigenic vaccination strategy

项目摘要

A lung cancer vaccine based on exosomes of induced pluripotent stem cells ABSTRACT A critical challenge in lung cancer research is to develop innovative vaccines to protect against pulmonary malignancy. Recent efforts to develop lung cancer vaccines have largely failed, probably due to their focus on inducing immune responses against individual lung tumor-associated antigens. If a lung cancer vaccine targets multiple antigens present only in lung tumors, but not in normal adult tissues, the chance of success will be greatly improved. Induced pluripotent stem cells (iPSCs) are reprogrammed from somatic cells and have the capacity of self-renewing and developing into all cell types of the adult body. It is known that iPSCs and tumor cells share carcinoembryonic antigens that are absent in normal adult tissues. Lung tumors also contain a subpopulation of tumor-initiating cells (TICs) with high tumorigenicity and self-renewal capability that contribute to the resistance to conventional therapies. Exploiting the antigenic similarity between tumor cells and iPSCs, we propose to thoroughly investigate efficacy of a lung cancer vaccine composed of exosomes from murine iPSCs expressing granulocyte-macrophage colony stimulating factor (GM-CSF) as an immunostimulatory adjuvant (iPSC-exo). We hypothesize that iPSC-exo vaccination prevents lung tumorigenesis by triggering CD8+ T cell-dependent immune responses and eradicating lung TICs. In this grant, we will investigate this hypothesis in two clinically relevant, immunocompetent murine lung tumor models. Two specific aims are proposed: 1) Investigate the translational potential of iPSC-exo vaccination against lung cancer; 2) Elucidate the mechanism by which iPSC-exo vaccination prevents lung cancer. We believe that the success of proposed experiments will lead to clinical trials of a similar vaccine against human pulmonary malignancy.

基于诱导多能干细胞外泌体的肺癌疫苗