Therapeutic HPV vaccination for stage IB1 cervical cancer

IB1 期宫颈癌的治疗性 HPV 疫苗接种

基本信息

批准号：
7664338
负责人：
Cornelia L Trimble
金额：
$ 28.83万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7664338
关键词：
Alabama Antigens Cervix Uteri Characteristics Clinical Clinical Trials Clinical Trials Design Collaborations DNA Vaccines Data Detox Development Disease Dose Dysplasia Excision Frequencies Genotype Goals Gynecologic Oncology Group Gynecologic Pathology Human Papilloma Virus Vaccine Human Papillomavirus Human papillomavirus 16 Immune Immune response Immunologics Immunotherapeutic agent Intervention Intervention Studies Lesion Malignant Neoplasms Malignant neoplasm of cervix uteri Measures Mediating Medical Minority Molecular Needles Neoplasms Operative Surgical Procedures Outcome Patients Peripheral Peripheral Blood Lymphocyte Phase I Clinical Trials Play Primary Neoplasm Proteins Protocols documentation Reagent Recruitment Activity Regulation Reproduction spores Research Research Personnel Risk Role Route Safety Shapes Site Solid Neoplasm Specimen Staging T-Lymphocyte Testing Therapeutic Time Translating Tumor Antigens Universities Vaccination Vaccines Viral Antigens Woman care systems clinical care cohort design immune function immunogenicity immunoregulation lymph nodes multidisciplinary neoplastic novel particle patient population peripheral blood pre-clinical prognostic response safety testing standard of care tumor tumor immunology virology

Alabama Antigens Cervix Uteri Characteristics Clinical Clinical Trials Clinical Trials Design Collaborations DNA Vaccines Data Detox Development Disease Dose Dysplasia Excision Frequencies Genotype Goals Gynecologic Oncology Group Gynecologic Pathology Human Papilloma Virus Vaccine Human Papillomavirus Human papillomavirus 16 Immune Immune response Immunologics Immunotherapeutic agent Intervention Intervention Studies Lesion Malignant Neoplasms Malignant neoplasm of cervix uteri Measures Mediating Medical Minority Molecular Needles Neoplasms Operative Surgical Procedures Outcome Patients Peripheral Peripheral Blood Lymphocyte Phase I Clinical Trials Play Primary Neoplasm Proteins Protocols documentation Reagent Recruitment Activity Regulation Reproduction spores Research Research Personnel Risk Role Route Safety Shapes Site Solid Neoplasm Specimen Staging T-Lymphocyte Testing Therapeutic Time Translating Tumor Antigens Universities Vaccination Vaccines Viral Antigens Woman care systems clinical care cohort design immune function immunogenicity immunoregulation lymph nodes multidisciplinary neoplastic novel particle patient population peripheral blood pre-clinical prognostic response safety testing standard of care tumor tumor immunology virology

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项目摘要

DESCRIPTION (provided by applicant): Human papillomavirus (HPV)-associated neoplasia of the cervix presents a compelling opportunity to test antigen-specific vaccination because expression of two nonself, viral antigens, E6 and E7, are together functionally required to initiate and maintain neoplastic lesions, both high grade dysplasia (CIN2/3), the precursor to invasive cancer, and cancer. This phase I clinical trial will assess the safety, tolerability, and immunogenicity of particle-mediated epidermal delivery (PMED) of a DNA vaccine which is targeted at the HPV16 E7 antigen, pNGVL4a-CRT-E7(detox), in patients with operable Stage IB1 cervical cancer associated with HPV16, the HPV genotype most commonly associated with disease. Clinical grade vaccine has been manufactured by NCI RAID, and has been formulated for PMED vaccination. This trial will also present a unique opportunity to assess the tumor compartment for molecular evidence of mechanisms of immune regulation, in specimens obtained at the time of standard therapeutic resection. Although the central assumption in designing immunotherapeutic strategies is that eliciting effector immune responses specific for tumor associated antigens will result in clinical response, it is clear from measures of HPV-specific immune responses in patients with HPV disease that the presence of immune responses in the peripheral blood does not always correlate with outcome. Therefore in this trial we will assess not only the safety and immunogenicity of vaccination in this patient cohort, but also determine whether measures of immune regulation in the tumor compartment correlate with ability to respond to vaccination. We have a demonstrated track record in clinical trial design and execution in this patient population, which is disproportionately comprised of minority women who do not access the medical care system effectively. This protocol will translate early development supported by the NCI SPORE mechanism, and take advantage of a longstanding collaboration with GOG investigators at the University of Alabama. This phase I clinical trial will test safety, feasibility, and immunogenicity of needle- free particle-mediated vaccination with a therapeutic HPV vaccine, pNGVL4a- CRT-E7(detox), in patients with operable Stage IB1 cervical cancer. This trial will also present a unique opportunity to assess the tumor compartment for evidence of mechanisms of immune regulation, in specimens obtained at the time of standard therapeutic resection. Clinical grade vaccine has been manufactured by NCI RAID, in collaboration with PowderMed. This trial is a SPORE-GOG collaboration.

描述（由申请人提供）：子宫颈与人类乳头瘤病毒（HPV）相关的肿瘤症是一个令人信服的机会来测试抗原特异性疫苗接种，因为表达了两种非自然的病毒抗原，E6和E7，在功能上需要进行功能和维持Neoplastic病变，以及两个高级癌症，以及对癌症的高级癌症（均为癌症）（3）。这项I期临床试验将评估DNA疫苗的颗粒介导的表皮递送（PMED）的安全性，耐受性和免疫原性，该疫苗针对HPV16 E7抗原，PNGVL4A-CRT-E7（detox），与HPV16，HPV16，HPV相关的患者与HPV相关的患者，PNGVL4A-CRT-E7（detox），PNGVL4A-CRT-E7（detox）。临床级疫苗是由NCI RAID生产的，已配制了PMED疫苗接种。该试验还将为评估在标准治疗切除时获得的标本中评估免疫调节机制的分子证据的肿瘤室的独特机会。尽管设计免疫治疗策略的中心假设是，引发针对肿瘤相关抗原的效应效应的免疫反应将导致临床反应，但从HPV疾病患者的HPV特异性免疫反应的措施可以清楚地看出，外周血中存在免疫反应的患者并不总是与结果相关。因此，在这项试验中，我们不仅会评估该患者队列中疫苗接种的安全性和免疫原性，而且还确定肿瘤区室中免疫调节的测量是否与对疫苗接种的反应能力相关。在该患者人群中，我们在临床试验设计和执行方面有了良好的记录，这是不成比例的，由少数族裔妇女有效地访问医疗系统。该协议将翻译由NCI孢子机制支持的早期开发，并利用与阿拉巴马大学的GOG调查员长期合作。这项I期临床试验将在患有可撞击的IB1宫颈癌的患者中测试与治疗性HPV疫苗PNGVL4A-E7（Detox）的无颗粒介导的疫苗接种的安全性，可行性和免疫原性。该试验还将提供一个独特的机会，以评估在标准治疗切除时获得的标本中免疫调节机制的证据。 NCI RAID与Powdermed合作制造了临床级疫苗。这项试验是孢子-GOG的合作。