Clinical study of GMCI in Pancreatic Cancer

GMCI治疗胰腺癌的临床研究

基本信息

批准号：
7284150
负责人：
Estuardo Aguilar-Cordova
金额：
$ 37.67万
依托单位：
ADVANTAGENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-04 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7284150
关键词：
Accounting Acute Adenovirus Vector Adjuvant Aftercare Antigen-Presenting Cells Apoptosis Appendix Applications Grants Boston Cancer Etiology Cancer Patient Cancer Vaccines Cells Cessation of life Clinic Clinical Clinical Protocols Clinical Research Clinical Trials Clinical Trials Data Monitoring Committees Combined Modality Therapy Contracts Data Diagnosis Disease Dose Evaluation Excision Funding Future General Hospitals Genes Goals Grant HSV-Tk Gene Histologic Immune Immunotherapy Incidence Infiltration Inflammatory Response Injection of therapeutic agent Institution Lead Malignant neoplasm of pancreas Massachusetts Measurable Mediating Medical Research Medicine Modeling Necrosis Neoplasm Metastasis Operative Surgical Procedures Outcome Palliative Care Pancreas Pancreatic Adenocarcinoma Pathologic Pathology Patients Phase Phase I Clinical Trials Phase II Clinical Trials Population Process Prodrugs Property Protocols documentation Radiation Radiosurgery Range Recombinants Research Ethics Committees Research Personnel Resectable Review Committee Safety Site Specimen Standards of Weights and Measures Superantigens T-Lymphocyte Technology Testing Time Tissues Toxic effect Tumor Antigens Tumor Immunity United States National Institutes of Health Upper arm Writing cell killing chemotherapy clinical research site college cytotoxic improved in vivo neoplastic cell pancreatic neoplasm particle pre-clinical programs response transduction efficiency tumor uptake valacyclovir vector

项目摘要

DESCRIPTION (provided by applicant): Pancreatic adenocarcinoma is the fourth leading cause of cancer deaths in the US; with less than one-year median survival, it accounts for approximately 30,000 diagnoses and deaths per year. Multimodality therapy, including surgery, radiation and chemotherapy, have not made a significant impact on the outcome and serve mostly as palliation. Thus, new treatment approaches are desperately needed for pancreatic cancer. Advantagene has been developing technologies that may improve the outcome of these standard therapies. Advantagene's lead technology platform, Gene Mediated Cytotoxic Immunotherapy (GMCI(tm)), is an approach which generates a systemic tumor vaccine effect through local delivery of an adenoviral vector (AdV-tk) expressing HSV-tk (TK) when combined with standard therapies. This approach has shown activity in many preclinical tumor models and demonstrated safety with potential efficacy in Phase I and Phase II clinical trials. GMCI(tm) has not been clinically evaluated in pancreatic cancer. The hypothesis for the mechanism, supported by preliminary studies, involves TK-specific cytotoxic and immune-stimulatory properties: (1) local TK-mediated tumor cell killing is appropriate to induce a "danger" microenvironment, (2) radiation induces an acute inflammatory response that potentiates uptake and presentation of TK-released tumor associated antigens by antigen presenting cells, and (3) effector T cell stimulation is potentiated by a superantigen-like effect of the TK molecule. The clinical hypothesis is that the resultant anti-tumor immunity will decrease the incidence or significantly delay local progression and metastases in pancreatic cancer patients. Pancreatic cancer provides an opportunity to evaluate the cytotoxic and immunostimulatory activity of GMCI(tm) and correlate this with clinical outcome. This Phase 1 grant is to support the first Phase I clinical trial to apply this technology in pancreatic cancer (Aim 1 and 2) and evaluate biologic activity in tumor specimens after treatment (Aim 3). The primary goal of this Phase 1 application is to evaluate the safety of GMCI(tm) with AdV-tk in pancreatic cancer and to evaluate vector function in pancreatic cancer in vivo. The hypothesis is that a safe and active vector dose will be identified that can be evaluated in a subsequent Phase II trial. The Phase II trial is the subject of the Phase 2 portion of this Fast-track application.

描述（由申请人提供）：胰腺腺癌是美国癌症死亡的第四个主要原因；中位生存期少于一年，每年约占诊断和死亡人数约30,000。多模式治疗，包括手术，放射线和化学疗法，并未对结果产生重大影响，并且主要用作抑制。因此，胰腺癌迫切需要新的治疗方法。 Advantagene一直在开发可能改善这些标准疗法结果的技术。 Advantagene的铅技术平台，基因介导的细胞毒性免疫疗法（GMCI（TM））是一种方法，当与标准疗法结合时，通过局部传递表达HSV-TK（TK）来通过局部递送腺病毒载体（ADV-TK）产生全身性肿瘤疫苗。这种方法在许多临床前肿瘤模型中都表明了活性，并在I期和II期临床试验中表现出具有潜在功效的安全性。 GMCI（TM）尚未在胰腺癌中进行临床评估。 The hypothesis for the mechanism, supported by preliminary studies, involves TK-specific cytotoxic and immune-stimulatory properties: (1) local TK-mediated tumor cell killing is appropriate to induce a "danger" microenvironment, (2) radiation induces an acute inflammatory response that potentiates uptake and presentation of TK-released tumor associated antigens by antigen presenting cells, and （3）效应T细胞刺激通过TK分子的超抗原样作用增强。临床假设是，由此产生的抗肿瘤免疫会降低胰腺癌患者的局部进展和转移量的局部进展和转移。胰腺癌提供了评估GMCI（TM）的细胞毒性和免疫刺激活性的机会，并将其与临床结果相关联。该第1阶段赠款是为了支持第一阶段临床试验，将该技术应用于胰腺癌（AIM 1和2），并在治疗后评估肿瘤标本中的生物学活性（AIM 3）。该第1阶段应用的主要目的是评估胰腺癌中GMCI（TM）的安全性，并评估体内胰腺癌的载体功能。假设是将确定可以在随后的II期试验中评估的安全且活跃的载体剂量。 II期试验是此快速轨道应用程序第2阶段部分的主题。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Therapeutic endoscopic ultrasonography: intratumoral injection for pancreatic adenocarcinoma.

治疗性内窥镜超声检查：胰腺腺癌的瘤内注射。

DOI：
10.1155/2013/207129
发表时间：
2013
期刊：
Gastroenterology research and practice
影响因子：
2
作者：
Shirley,LawrenceA;Aguilar,LauraK;Aguilar-Cordova,Estuardo;Bloomston,Mark;Walker,JonP
通讯作者：
Walker,JonP