TCR Affinity and Therapeutic Efficacy of T Cells

T 细胞的 TCR 亲和力和治疗效果

基本信息

批准号：
7939349
负责人：
MICHAEL I. NISHIMURA
金额：
$ 12.29万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7939349
关键词：
APC Vaccine Address Adenoviruses Adoptive Cell Transfers Advanced Malignant Neoplasm Affinity Animal Model Animals Antigen Targeting Antigens Autologous Biological Assay Blood CD4 Positive T Lymphocytes CD8B1 gene Cancer Patient Cancer Vaccines Cells Clinical Clinical Trials Clinical Trials Design Dendritic Cells Disseminated Malignant Neoplasm Engineering Epitopes Frequencies Gene Transfer Gene-Modified Genes Goals HLA-A2 Antigen Human Immune Immune response Immunotherapy In Vitro Interleukin-2 Malignant Neoplasms Mediating Memory Methodology Modeling Monophenol Monooxygenase Mus Patients Peptides Prevention Recombinants Reporting Retroviral Vector Safety Source Specificity T-Lymphocyte Treatment Efficacy Treatment Protocols Tumor Antigens Tumor Cell Derivative Vaccine Vaccinated Vaccination Vaccines Vaccinia virus Variant base cellular engineering chemotherapy cytokine design improved in vivo interest loss of function melanoma neoplastic cell peripheral blood plasmid DNA pre-clinical prevent response treatment strategy tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): The identification of T cell antigens expressed by human tumors has led to the clinical trials designed to boost the host immune response against their tumors (reviewed by 1-4). Cancer vaccine strategies include antigenic peptides, peptide loaded dendritic cells, recombinant adenoviruses, vaccinia viruses, and plasmid DNA. Despite evidence of vaccination, very few clinical responses have been reported. Furthermore, those patients which had a clinical response generally have no evidence of vaccination. We have recently described a TCR gene transfer a treatment strategy designed to provide a source of autologous tumor reactive T cell to any patient regardless of their immune status. The primary goal of this proposal is to determine TCR gene modified T cells can be safely administered and have anti-tumor efficacy using an animal model for human melanoma. We will also determine how TCR affinity, tumor antigen vaccines, and IL-2 impacts on the safety and efficacy of TCR gene modified T cells in vivo. In addition to safety and efficacy, we will use using sensitive PCR assays we developed to address relevant questions regarding the fate of adoptively transferred T cells in tumor bearing mice which are not easily addressed in cancer patients. The successful completion of the proposed studies will enable us to design better immunotherapy treatment strategies for patients with advanced cancer.

描述（由申请人提供）：人类肿瘤表达的T细胞抗原的鉴定导致临床试验旨在增强对其肿瘤的宿主免疫反应（1-4综述）。癌症疫苗策略包括抗原肽，肽负载的树突状细胞，重组腺病毒，疫苗病毒和质粒DNA。尽管有疫苗接种的证据，但很少有临床反应报道。此外，那些具有临床反应的患者通常没有疫苗接种的证据。我们最近描述了TCR基因转移一种治疗策略，旨在为任何患者提供自体肿瘤反应性T细胞的来源，无论其免疫状态如何。该提案的主要目的是确定可以安全地施用TCR基因修饰的T细胞，并使用人黑色素瘤的动物模型具有抗肿瘤功效。我们还将确定TCR亲和力，肿瘤抗原疫苗和IL-2如何影响TCR基因修饰的T细胞在体内的安全性和有效性。除了安全性和疗效外，我们还将使用我们开发的敏感PCR分析来解决有关肿瘤轴承小鼠的命运的相关问题，这些问题在癌症患者中不易解决。拟议研究的成功完成将使我们能够为晚期癌症患者设计更好的免疫疗法治疗策略。