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Development of a targeted delivery platform for checkpoint inhibitors

检查点抑制剂靶向递送平台的开发

基本信息

批准号：
9756345
负责人：
Kun Cheng
金额：
$ 34.39万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9756345
关键词：
Adopted Affinity Antibodies Bacteriophages Binding Biodistribution Blood Blood Circulation CD34 gene CT26 Cancer Patient Cells Cleaved cell Clinical Trials Colon Carcinoma DU145 Development Distal Effectiveness Enzymes FDA approved FOLH1 gene Future Goals Growth Human Immune checkpoint inhibitor Immunotherapy Implant In Vitro Inbred BALB C Mice LNCaP Ligands Link Lymphoma Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of prostate Malignant neoplasm of urinary bladder Mediating Modeling Molecular Weight Mus Neoplasm Metastasis Normal Cell Normal tissue morphology Nude Mice PC3 cell line PD-1/PD-L1 PDCD1LG1 gene Penetration Peptides Pharmaceutical Preparations Prostatic Neoplasms Reporting Research Serum Solid Neoplasm Specificity Stimulus Therapeutic Effect Tissues Toxicology Treatment Efficacy anti-PD-L1 anti-cancer antibody inhibitor antitumor effect base cancer cell cancer immunotherapy cancer therapy castration resistant prostate cancer humanized mouse immune checkpoint immunogenicity improved in vivo inhibitor/antagonist interest interstitial melanoma mouse model neoplastic cell novel prostate cancer cell prostate cancer model protein aminoacid sequence receptor side effect small molecule synthetic peptide targeted delivery tumor tumor microenvironment

项目摘要

Abstract The goal of this proposed research is to develop a targeted delivery platform for checkpoint inhibitors. The platform will contain a targeting ligand, an enzyme-responsive linker, and a peptide- based checkpoint inhibitor. We recently discovered several peptide-based PD-L1 inhibitors that can be potentially used for cancer immunotherapy. In this study, we will evaluate the platform in an advanced prostate cancer model. Particularly, we propose to link a PSMA-specific ligand to the anti-PD-L1 peptides via a PSA-cleavable linker. The overall objectives of this project are: 1) to develop a targeted anti-PD-L1 peptide for cancer immunotherapy; 2) to evaluate its therapeutic effect using humanized mice implanted with human castration-resistant prostate cancer (CRPC) cells. The long-term goal of the project is to develop a targeted peptide-based platform for cancer immunotherapy. Our central hypothesis is that cancer growth and metastasis can be effectively inhibited by targeted delivery of anti-PD-L1 peptides to cancer cells. At the completion of this project, we expect to pave the way for the future development of a targeted PD-L1 inhibitor for cancer immunotherapy. Successful completion of the proposed studies is also expected to provide a peptide-based platform (by changing the targeting ligand and the tissue-specific linker) for other peptide-based checkpoint inhibitors.

摘要