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.

抽象的胰腺癌 (PC) 的全球年发病率超过 495,000 例，并且年死亡率近46万例。大多数患者诊断较晚且无法接受切除术，因此依靠药物治疗来延长生命。当前的疗法只能提供有限的益处，这在很大程度上是由于周围的致密基质组织并保护肿瘤。 Duo Oncology 正在开发一种超小纳米颗粒，其中包含：吉西他滨和免疫调节趋化因子受体 2 型拮抗剂可杀死癌症细胞并增强抗肿瘤免疫力。这些小于 30nm 的小纳米粒子直径，显示出增强的外渗和组织渗透，特别是在 PC 肿瘤中富含致密的基质。此外，本文提出的研究将为 DUO-307 的未来做好准备使用 IND 技术进行配方优化、毒理学和治疗效果研究最先进的离体肿瘤外植体模型和临床相关的 PC 小鼠模型致密的基质。