权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

ERB 2NEU DNA VACCINES FOR BREAST CANCER IMMUNOTHERAPY

用于乳腺癌免疫治疗的 ERB 2NEU DNA 疫苗

基本信息

批准号：
6512857
负责人：
Thomas J Kipps
金额：
$ 22.05万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-09-01 至 2003-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6512857
关键词：
antigen presenting cell breast neoplasms cytotoxic T lymphocyte disease /disorder model gene expression gene therapy genetically modified animals immune tolerance /unresponsiveness laboratory mouse leukocyte activation /transformation neoplasm /cancer immunotherapy neoplasm /cancer transplantation neoplasm /cancer vaccine protooncogene tissue /cell culture transfection vector vaccine

项目摘要

DESCRIPTION (Adapted from the Investigator's Abstract): This project evaluates the potential of erb B-2/neu immunotherapy for neoplastic disease using DNA vaccines in mice transgenic for the non-activated rat neu oncogene. These mice uniformly develop mammary tumors that express high levels of neu, and thus serve as a model for patients with cancers that overexpress erb B-2, the human neu homologue. The investigators have made plasmid vectors encoding erb B-2 (pErb B-2) or rat neu (Pneu) that induce immune responses to erb B-2 or neu when injected into muscle (IM) or dermis (ID). The investigators have found that pNeu can induce protective immunity in FVB/N non-Tg mice from the adoptive transfer of otherwise syngeneic neu- expressing mammary tumors derived from FVB/N neu-Tg mice. However, they also find that FVB/N mice have an H-2 haplotype associated with a poor immune response potential to pErbB-2/neu DNA vaccines, arguably limiting their capacity to break self-tolerance to neu in FVB/N neu-Tg mice. They have bred the neu transgene onto strains of mice that have a high response potential to pErb B-2 and pNeu (e.g. BALB/c). Preliminary studies indicate that self-tolerance to neu can be broken in neu-Tg mice with the H-2d haplotype by ID injections of pErbB-2. Work done in parallel on this project has developed improved strategies for inducing desired immune responses against the antigens encoded by DNA vaccines. The investigators find that plasmids that encode chimeric antigens that are targeted for rapid proteasome-dependent degradation are significantly more efficient in inducing specific cytotoxic T lymphocyte ( CTL) responses than conventional DNA vaccines. In addition they have found that co-injection of a DNA vaccine with the plasmid encoding the CD40-ligand (CD154) can significantly improve the immune response to a transgene antigen. They will test whether these strategies enhance their ability to break self-tolerance to neu and induce protective immunity against de novo or adoptively transferred neu-expressing mammary tumors in neu-Tg mice. In addition they will compare the relative efficacy of such DNA vaccines strategies with that of using erbB-2/neu peptide-pulsed antigen presenting cells to induce CTL against syngeneic cells expressing high levels of the erb B-2/neu proto-oncogene.

描述(改编自《调查者摘要》)：本项目评估erb B-2/neu免疫治疗肿瘤疾病的潜力 DNA疫苗在转基因未激活大鼠神经细胞中的应用致癌基因。这些小鼠都会出现高表达的乳腺肿瘤。 Neu水平，因此可以作为癌症患者的模型过度表达人类neu同源基因erb B-2。调查人员已经做出了编码erb B-2(PERB B-2)或大鼠Neu(Pneu)的质粒载体可诱导肌肉或真皮注射erb B-2或neu的免疫反应 (ID)。研究人员发现，pneu可以诱导保护性免疫。在FVB/N非TG小鼠中过继转移其他同基因neu-1 表达FVB/N neu-TG小鼠来源的乳腺肿瘤。然而，他们还发现FVB/N小鼠具有与不良相关的H-2单倍型 PErbB-2/neu DNA疫苗的免疫应答潜力，可以说是有限的它们在FVB/N neu-TG小鼠中打破对neu的自我耐受的能力。他们已经将neu转基因基因培育到了具有高反应性的小鼠品系上对PERB B-2和Pneu的潜力(例如BALB/c)。初步研究表明在带有H-2d的neu-TG小鼠中，对neu的自我耐受可以被打破通过ID注射pErbB-2进行单倍型。在此基础上并行完成的工作该项目已经开发出了诱导所需免疫的改进策略对DNA疫苗编码的抗原的反应。调查人员发现编码嵌合抗原的质粒是快速反应的目标依赖蛋白酶体的降解显著更有效地诱导特异性细胞毒性T淋巴细胞(CTL)反应优于常规 DNA疫苗。此外，他们还发现，联合注射DNA 编码CD40配体(CD154)的疫苗可显著提高对转基因抗原的免疫反应。他们将测试是否这些策略增强了他们打破对Neu和Neu的自我容忍的能力诱导对从头感染或过继转移的保护性免疫 Neu-tg小鼠中neu表达的乳腺肿瘤。此外，他们还将比较这类DNA疫苗策略与使用的相对有效性 ErbB-2/neu多肽冲击的抗原提呈细胞诱导CTL抗高表达erb B-2/neu原癌基因的同基因细胞。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Efficient infection of a human T-cell line and of human primary peripheral blood leukocytes with a pseudotyped retrovirus vector.

用假型逆转录病毒载体有效感染人类 T 细胞系和人类原代外周血白细胞。

DOI：
10.1073/pnas.93.21.11842
发表时间：
1996
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Sharma,S;Cantwell,M;Kipps,TJ;Friedmann,T
通讯作者：
Friedmann,T

Deoxyribonucleic acid vaccines encoding antigens with rapid proteasome-dependent degradation are highly efficient inducers of cytolytic T lymphocytes.

编码具有快速蛋白酶体依赖性降解的抗原的脱氧核糖核酸疫苗是溶细胞性 T 淋巴细胞的高效诱导剂。