Developing MRI-Guided Preventive Dendritic Cell Vaccination Strategy to Avoid Post-surgical Pancreatic Cancer Recurrence and Metastasis

制定 MRI 引导的预防性树突状细胞疫苗接种策略以避免术后胰腺癌复发和转移

• 批准号: 10728509
• 负责人: Vahid Yaghmai
• 金额: $ 39.25万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728509
• 关键词: Abdomen; Adjuvant; Affect; Biodistribution; Cancer Etiology; Cells; Chemotherapy and/or radiation; Clinic; Clinical; Colorectal Neoplasms; Combined Modality Therapy; Dendritic Cell Vaccine; Dendritic Cells; Dose; Excision; Funding; Genetic Heterogeneity; Genetically Engineered Mouse; Guidelines; Heparin; Homing; Image; Immunotherapy; Implant; Individual; Intraperitoneal Injections; KPC model; Kidney Neoplasms; Label; Liver neoplasms; Lymphoid Tissue; Magnetic Resonance Imaging; Magnetism; Malignant neoplasm of pancreas; Maps; Measurement; Methods; Monitor; Mus; National Comprehensive Cancer Network; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Paclitaxel; Pancreatic Ductal Adenocarcinoma; Patients; Peer Review; Postoperative Period; Prediction of Response to Therapy; Predisposition; Preventive; Primary Neoplasm; Protamines; Publications; Recommendation; Recurrence; Recurrent Malignant Neoplasm; Recurrent tumor; Role; Route; Solid; Stomach Neoplasms; Subcutaneous Injections; Tail; Techniques; Testing; Therapeutic; Time; Tissues; Titrations; Transgenic Organisms; Translating; Treatment Efficacy; United States National Institutes of Health; Uterine Neoplasms; Vaccine Therapy; Vaccines; Veins; Work; anti-tumor immune response; body system; cancer recurrence; cancer therapy; chemoradiation; chemotherapy; clinical application; clinical efficacy; clinical translation; curative treatments; dendritic cell vaccination; early detection biomarkers; ferumoxytol; gemcitabine; high risk; imaging biomarker; implantation; improved; in vivo; individual patient; intraperitoneal; lymph nodes; migration; mortality; mouse model; nanocomplexes; neoplastic cell; novel; novel strategies; pancreatic ductal adenocarcinoma model; pancreatic neoplasm; predicting response; predictive marker; prevent; relapse prevention; response; success; translational model; treatment response; treatment strategy; tumor; tumor growth; vaccination strategy; vaccine efficacy; vaccine response

PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer mortality in the US. Surgical resection is the only curative treatment, and due to the high recurrence rate (60%), only 20% survive five years. Chemotherapy and radiotherapy after surgical resection only offer modest improvements in survival. A new approach to prevent tumor recurrence in PDAC patients is urgently needed. We will compare overall survival (OS) after tumor resection between the combination of dendritic cell (DC) vaccination via an improved intraperitoneal, i.p., route, combined with current therapy (gemcitabine), versus the use of preventive DC vaccination alone or gemcitabine alone (Aim 1). Given the relationship between migration to lymph nodes (LNs) and anti-tumor immune response, accurate quantification of DC vaccine migration could serve as an early biomarker for predicting longitudinal response (OS) and elucidating the cause of differential response rates between patients. Understanding factors that affect DC vaccine response rates will enable the titration of vaccine doses to optimize outcomes for individual patients. Thus, we will validate magnetic imaging via quantitative susceptibility mapping (QSM) and ultrashort echo time (UTE) R2* techniques for tracking clinically applicable magnetic-labeled DC vaccines to draining abdominal LNs (Aim 2). We will test whether advanced MRI-tracked DC vaccine homing to LNs can be used as an early imaging biomarker to predict OS of the combination of DC vaccination and gemcitabine treatment post-surgery (Aim 3). The proposed work will meet the significant demand for a novel DC vaccination strategy of cancer therapy that can rapidly be translated to the clinic to prevent relapse after pancreatic tumor surgery while adding an imaging biomarker as a potentially powerful method to simultaneously predict response to the therapy. The success of the proposed preventive DC vaccination strategy and prediction of response to treatment could have a broad impact as a clinical extension to other solid organ systems (e.g., stomach, liver, colorectal, renal, or uterine tumors) as novel adjuvant immunotherapy to prevent relapse after surgery.

项目总结

项目成果

Dendritic cells in pancreatic cancer immunotherapy: Vaccines and combination immunotherapies.

• DOI: 10.1016/j.prp.2019.152691
• 发表时间: 2019-12
• 期刊: Pathology, research and practice
• 作者: Jia Yang;J. Shangguan;A. Eresen;Yu Li;Jian Wang;Zhuoli Zhang

Exploring the landscape, hot topics, and trends of bariatric metabolic surgery with machine learning and bibliometric analysis.

• DOI: 10.1177/26317745221111944
• 发表时间: 2022-01
• 期刊: THERAPEUTIC ADVANCES IN GASTROINTESTINAL ENDOSCOPY
• 影响因子: 2.6
• 作者: Song, Yancheng;Ni, Zhenni;Li, Yi;Li, Zhaopeng;Zhang, Jian;Guo, Dong;Yuan, Chentong;Zhang, Zhuoli;Li, Yu
• 通讯作者: Li, Yu

Natural killer cell-based adoptive transfer immunotherapy for pancreatic ductal adenocarcinoma in a KrasLSL-G12D p53LSL-R172H Pdx1-Cre mouse model.

• 发表时间: 2019-08
• 期刊: American journal of cancer research
• 影响因子: 5.3
• 作者: Su Hu;Jia Yang;J. Shangguan;A. Eresen;Yu Li;Q. Ma;V. Yaghmai;Yuri S. Velichko;Chunhong Hu;Zhuoli Zhang

Establishment of a new non-invasive imaging prediction model for liver metastasis in colon cancer.

• 发表时间: 2019
• 期刊: American journal of cancer research
• 影响因子: 5.3
• 作者: Yu Li;A. Eresen;J. Shangguan;Jia Yang;Yun Lu;Dong Chen;Jian Wang;Yury Velichko;V. Yaghmai;Zhuoli Zhang