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Image-guided Interventional Combination Liver Cancer Immunotherapy

影像引导介入性肝癌联合免疫治疗

基本信息

批准号：
10569648
负责人：
Vahid Yaghmai
金额：
$ 36.13万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10569648
关键词：
Adoptive Transfer Apoptosis BAY 54-9085 Biodistribution Biological Markers Cancer Etiology Cancer Patient Cell Proliferation Cessation of life Characteristics Clinical Contrast Media Detection Diameter Dose Excision FDA approved Goals Heparin Homing Immunotherapy In Vitro Infusion procedures Label Lead Liver Liver neoplasms Magnetic Resonance Imaging Magnetism Malignant Neoplasms Malignant neoplasm of liver Maps Measurement Methods Microspheres Monitor Natural Killer Cell Immunotherapy Natural Killer Cells Operative Surgical Procedures Oral Oral Administration Outcome Patients Pharmaceutical Preparations Pilot Projects Placebos Portal vein structure Prediction of Response to Therapy Predisposition Primary carcinoma of the liver cells Protamines Rattus Reference Standards Regimen Rodent Model Serum Systemic Therapy Therapeutic Transplantation Treatment Efficacy Tumor Tissue United States Vascular blood supply Visualization cancer immunotherapy cancer therapy cell motility clinical application curative treatments cytotoxic cytotoxicity detection sensitivity early detection biomarkers ferumoxytol image guided image guided intervention imaging properties improved in vivo indexing individual patient intrahepatic kinase inhibitor liver cancer model migration nanocomplexes nanosized neoplastic cell phantom model predictive tools quantitative imaging responders and non-responders response side effect success tablet formulation therapy outcome time interval tool trafficking transcatheter arterial chemoembolization treatment response tumor tumor specificity uptake

项目摘要

PROJECT SUMMARY For clinical application, a critical remaining hurdle for natural killer (NK) cell-based adoptive transfer immunotherapy (ATI) is the inadequate homing efficiency of ex vivo-expanded effector NKs to the targeted tumor tissues. Another significant obstacle is the lack of well-established non-invasive tools for monitoring NK cell trafficking to tumor tissues. Currently, NK cell-based ATI (NK-ATI) responders or non-responders are identified by changes in serum biomarkers or tumor size, both of which may not occur until weeks or months after therapy initiation. Serial monitoring of NK cell migration to tumors during ATI could alternatively serve as an important early biomarker for timely prediction of longitudinal response, thus affording early adjustments to each individual patient’s therapeutic regimen. Recently, our studies have demonstrated that sorafenib not only inhibits tumor cell proliferation, but also promotes antitumor activity of NKs. Therefore, concurrent administration of sorafenib may be critical for sustained NK activation and cytotoxicity. We have developed biodegradable sorafenib-eluting microsphere (SEM, with a diameter of 492 ± 34 nm; nano-SEM) delivery platforms that significantly increase therapeutic efficacy via image-guided transcatheter IHA delivery. We will develop a new image-guided interventional combination liver cancer immunotherapy approach including a) image-guided transcatheter IHA infusion of NKs directly into the blood supply of targeted liver tumor(s) and b) concurrent infusion of nano-SEMs to enhance sorafenib therapeutic efficacy (with minimal side effects) and to strengthen NK antitumor activity.

项目总结