TRANSFORMING GENES AND IMMUNOLOGICAL TUMOR REGRESSION

转化基因和免疫肿瘤消退

• 批准号: 6376405
• 负责人: Hans Schreiber
• 金额: $ 64.47万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6376405
• 关键词: neoplasm /cancer immunology; neoplasm /cancer remission /regression; neoplastic transformation

Transforming genes are essential for the development of cancer, and some of these genes encode strong antigens that can elicit tumor regression by CD+ T cells. One common goal of this Project is the identification of CTL- recognized peptide epitopes on antigens with such oncological and immunological, i.e. antigens encoded by human papilloma virus (HPV) and antigens found experimentally induced murine tumors. An additional goal of this Project is to understand how these CTL epitopes can be most effectively presented to the immune system. A final goal is to understand how cancer escape immune responses to these transforming proteins. Dr. Kast will explore the use of virus-like particles (VLPs) to immunize against products of transforming genes and plans to induce murine and human CD8+ T cells to transforming proteins of HPV, a major causative agent of human cervical cancer. Using experimental tumors as models, Dr. Schreiber will determine whether the unique antigens that are the prominent rejection antigen on chemically and physically induced tumors are due to somatic mutations (and thus truly tumor-specific), whether these mutant proteins have significance in the malignant process and whether unique antigens that are lost from and those that are retained by progressor tumors differ in oncogenic efforts in immunogenicity. Dr. Argon will explore the cell-biological mechanisms that allows hat-shock proteins to bind and traffic viral or tumor-specific mutant peptides and "deliver" them to the MHC Class I molecules for presentation to CD8+ T cells. Finally, Dr. Meredith will give advice and guidance on the multiple biochemical aspects of the program and produce essential reagents. Together the three projects will define conditions and mechanism by which CD8+ T cell responses to peptides encoded by transforming genes lead to tumor destruction.

转化基因对癌症的发展至关重要， 这些基因编码强抗原，可以引起肿瘤消退， CD+ T细胞。该项目的一个共同目标是确定CTL- 具有这种肿瘤学和免疫学特性的抗原上的识别的肽表位 免疫学的，即由人乳头瘤病毒（HPV）编码的抗原，以及 实验发现的抗原诱导小鼠肿瘤。另一个目标是 这个项目是为了了解这些CTL表位是如何被最 有效地呈现给免疫系统。最后一个目标是了解 癌症是如何逃避对这些转化蛋白的免疫反应的。博士 卡斯特将探索使用病毒样颗粒（VLP）免疫 针对转化基因的产物，并计划诱导小鼠和 人CD 8 + T细胞转化HPV的蛋白，这是一个主要的致病因素， 人宫颈癌的病原体。使用实验肿瘤作为模型，博士。 Schreiber将确定是否是独特的抗原， 化学和物理诱导肿瘤的显著排斥抗原 是由于体细胞突变（因此真正的肿瘤特异性），无论 这些突变蛋白在恶性过程中具有重要意义， 是否有独特的抗原丢失和保留， 进展肿瘤在免疫原性的致癌作用方面不同。阿尔贡医生 将探索细胞生物学机制， 以结合和运输病毒或肿瘤特异性突变肽并“递送” 将它们与MHC I类分子结合以呈递给CD 8 + T细胞。 最后，梅雷迪思博士将提供建议和指导的多个 生物化学方面的计划和生产必要的试剂。 这三个项目将共同确定条件和机制， CD 8 + T细胞对转化基因编码的肽的应答导致 肿瘤破坏

项目成果

Pharmacokinetic differences between a T cell-tolerizing and a T cell-activating peptide.

T 细胞耐受肽和 T 细胞激活肽之间的药代动力学差异。

• DOI: 10.4049/jimmunol.166.12.7151
• 发表时间: 2001
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Weijzen,S;Meredith,SC;Velders,MP;Elmishad,AG;Schreiber,H;Kast,WM
• 通讯作者: Kast,WM

Tracking the common ancestry of antigenically distinct cancer variants.

追踪抗原不同的癌症变异的共同祖先。

• 发表时间: 2001
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Schreiber,K;Wu,TH;Kast,WM;Schreiber,H
• 通讯作者: Schreiber,H

Point mutation in essential genes with loss or mutation of the second allele: relevance to the retention of tumor-specific antigens.

• DOI: 10.1084/jem.194.3.285
• 发表时间: 2001-08-06
• 期刊: The Journal of experimental medicine
• 作者: Beck-Engeser GB;Monach PA;Mumberg D;Yang F;Wanderling S;Schreiber K;Espinosa R 3rd;Le Beau MM;Meredith SC;Schreiber H
• 通讯作者: Schreiber H