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A novel dual-carrier ultrasmall nanomedicine for the treatment of stroma-rich pancreatic cancer

一种用于治疗富含基质的胰腺癌的新型双载体超小纳米药物

基本信息

批准号：
10759720
负责人：
Katherine Marie Eichinger
金额：
$ 39.5万
依托单位：
DUO ONCOLOGY INC
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：
2023-09-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10759720
关键词：
Abbreviations Address Antioxidants Automobile Driving Biodistribution Blood Cell Count CCL2 gene CCL7 gene CD8B1 gene Cells Cessation of life Chemistry Chemotaxis Clinical Chemistry Combined Modality Therapy Data Diagnosis Diameter Disease Disease Progression Dose Environment Excision Extravasation Formulation Future Goals Immune Immune Evasion Immune checkpoint inhibitor Immune response Immuno-Chemotherapy In Vitro In complete remission Incidence Intravenous KPC model KRASG12D Legal patent Licensing Malignant Neoplasms Malignant neoplasm of pancreas Maximum Tolerated Dose Medical Modeling Mus Oncology Organ Pathway interactions Patients Penetration Peptide Hydrolases Pharmaceutical Chemistry Pharmacotherapy Phase Phenotype Pilot Projects Polymers Pre-Clinical Model Prodrugs Production Reporting Research Resistance Small Business Innovation Research Grant Solid Neoplasm Survival Rate Therapeutic Tissues Toxic effect Toxicokinetics Toxicology Treatment Efficacy Tumor Immunity Tumor-Infiltrating Lymphocytes Tumor-associated macrophages Universities Up-Regulation antagonist cancer cell cancer therapy checkpoint therapy chemokine chemokine receptor clinically relevant cytotoxic cytotoxicity efficacy evaluation efficacy testing gemcitabine immune modulating agents immunoregulation in vivo innovation monocyte mortality mouse model nanomedicine nanoparticle neoplastic cell novel pancreatic cancer model pancreatic cancer patients phase 1 study pre-Investigational New Drug meeting prognostic receptor recruit standard of care success therapy resistant tumor tumor growth tumor microenvironment

项目摘要

Abstract Pancreatic cancer (PC) has an annual worldwide incidence of more than 495,000 cases and an annual mortality rate of almost 460,000 cases. Most patients are diagnosed late and cannot undergo resection and therefore rely on pharmacotherapy to extend their lives. Current therapies offer only limited benefit due in large part to the dense stroma tissue that surrounds and protects the tumor. Duo Oncology is developing an ultra-small nanoparticle containing, gemcitabine and an immunomodulatory chemokine receptor type 2 antagonist to kill cancer cells and invigorate anti-tumor immunity. These small nanoparticles, less than 30nm in diameter, show enhanced extravasation and tissue penetration, particularly in the PC tumors enriched with dense stroma. Further, research proposed herein will prepare DUO-307 for future IND-enabling studies with formulation optimization, toxicology, and therapeutic efficacy using a cutting edge ex vivo tumor explant model and a clinically-relevant mouse model of PC with dense stroma.

摘要胰腺癌（PC）在全球范围内的年发病率超过495，000例，年死亡率近46万例。大多数患者确诊较晚，接受切除手术，因此依靠药物治疗来延长生命。电流治疗仅提供有限的益处，保护肿瘤。Duo Oncology正在开发一种超小纳米颗粒，吉西他滨和免疫调节趋化因子受体2型拮抗剂杀死癌症细胞和增强抗肿瘤免疫力。这些小纳米颗粒，小于30纳米，直径，显示增强的外渗和组织渗透，特别是在PC肿瘤中富含致密基质。此外，本文提出的研究将为未来的DUO-307做好准备。 IND使能性研究，包括使用尖端离体肿瘤外植体模型和PC的临床相关小鼠模型，致密基质。