Adoptive T cell Therapy for Patients with NY-ESO-1 Expressing Sarcomas

表达 NY-ESO-1 肉瘤患者的过继 T 细胞治疗

基本信息

批准号：
9131646
负责人：
Seth M Pollack
金额：
$ 17.17万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9131646
关键词：
Adoptive Immunotherapy Adoptive Transfer Aftercare Allogenic Antigen Presentation Antigens Atypical lymphocyte Autologous Biopsy Blocking Antibodies Blood CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene CTAG1 gene Cancer Immunology Science Cell Separation Cell physiology Clinical Clinical Research Clinical Trials Cyclophosphamide Data Data Analyses Dose Engineering Enrollment Environment Foundations Fred Hutchinson Cancer Research Center Future Gene Transfer Goals Hematopoietic Stem Cell Transplantation Human Immune Immune system Immunology Immunotherapeutic agent Immunotherapy In Vitro Infiltration Infusion procedures Interferon Type II Interleukin-2 Laboratories Laboratory Study MHC Class II Genes Malignant Neoplasms Mentors Methodology Methods Modality Myxoid/Round Cell Liposarcoma Operative Surgical Procedures Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phase Pilot Projects Population Principal Investigator Proteins Regimen Research Research Personnel Robin bird Running Safety Signal Pathway Solid Neoplasm T cell therapy T-Cell Receptor T-Cell Receptor Genes T-Lymphocyte Testing Therapeutic Therapy trial Toxic effect Training Translational Research Treatment Failure Vaccines Variant Writing arm base cancer immunotherapy career clinical care conditioning design experience genotoxicity immunogenic improved in vivo leukemia melanoma neoplasm immunotherapy neoplastic cell novel partial response patient oriented phase I trial pre-clinical preclinical study preconditioning receptor expression sarcoma senior faculty success synovial sarcoma translational study treatment strategy tumor tumor progression

Adoptive Immunotherapy Adoptive Transfer Aftercare Allogenic Antigen Presentation Antigens Atypical lymphocyte Autologous Biopsy Blocking Antibodies Blood CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene CTAG1 gene Cancer Immunology Science Cell Separation Cell physiology Clinical Clinical Research Clinical Trials Cyclophosphamide Data Data Analyses Dose Engineering Enrollment Environment Foundations Fred Hutchinson Cancer Research Center Future Gene Transfer Goals Hematopoietic Stem Cell Transplantation Human Immune Immune system Immunology Immunotherapeutic agent Immunotherapy In Vitro Infiltration Infusion procedures Interferon Type II Interleukin-2 Laboratories Laboratory Study MHC Class II Genes Malignant Neoplasms Mentors Methodology Methods Modality Myxoid/Round Cell Liposarcoma Operative Surgical Procedures Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phase Pilot Projects Population Principal Investigator Proteins Regimen Research Research Personnel Robin bird Running Safety Signal Pathway Solid Neoplasm T cell therapy T-Cell Receptor T-Cell Receptor Genes T-Lymphocyte Testing Therapeutic Therapy trial Toxic effect Training Translational Research Treatment Failure Vaccines Variant Writing arm base cancer immunotherapy career clinical care conditioning design experience genotoxicity immunogenic improved in vivo leukemia melanoma neoplasm immunotherapy neoplastic cell novel partial response patient oriented phase I trial pre-clinical preclinical study preconditioning receptor expression sarcoma senior faculty success synovial sarcoma translational study treatment strategy tumor tumor progression

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项目摘要

DESCRIPTION (provided by applicant): The candidate's career goal is to become a principal investigator (PI) of a translational immunology laboratory that will develop immunotherapeutic approaches towards the treatment of patients with advanced sarcoma. In the immediate term, the candidate aims to gain experience as a translational researcher by performing the studies outlined in this proposal. Central to this effort, the candidate will serve as the PI of the phaseI trial examining the use of autologous NY-ESO-1 specific CD8+ T cells for patient with advanced NY-ESO-1 expressing sarcomas in the context of a novel conditioning regimen which incorporates IFNγ. This is a trial that the candidate has written, designed and developed much of the preclinical foundation for. By serving as PI for this trial, the candidate will gain experiece in conducting an adoptive immunotherapy trial, and gain experience collecting and analyzing data from this trial. Additionally, the trial will serve as the platform to initiate multiple labortory-based translational studies investigating mechanisms of immune escape for patients on the trial and strategies to improve successor trials. The trial will be conducted at the Fred Hutchinson Cancer Research Center, an ideal environment for clinical and translational research and a leader in the field of T-cell immunotherapy trials. Dr. Stanley Riddell, an internationally renowned expert in cancer immunology and adoptive T cell therapy trials who is also an experienced and successful mentor, will serve as the primary to mentor the candidate. The candidate has also assembled a mentoring team comprised of senior faculty each with internationally renowned expertise in their particular field of research: Robin Jones (expertise in sarcoma clinical care and clinical trials), Martin (Mac) Cheever (expertise in solid tumor immunotherapy trials) and Cassian Yee (expertise in antigen specific T cell therapy trials). The specific aims of the proposal are as follows: Aim 1: To evaluate in a Phase I trial, the toxicity, persistence and antitumor activity of autologous NY- ESO-1 specific CD8+ cells administered with a novel conditioning regimen incorporating IFNγ, Cyclophosphamide (CY) and low dose IL-2 for patients with advanced MRCL and SS. Aim 2: To evaluate the emergence of antigen loss variants and strategies to broaden the applicability and enhance antigenicity of SS and MRCL patients receiving adoptive T cell therapy. Aim 3: To evaluate strategies to isolate NY-ESO-1 specific CD4+ T-cells for adoptive therapy to enhance or maintain CD8+ T cell function.

描述（由适用提供）：候选人的职业目标是成为转化免疫学实验室的首席研究员（PI），该研究人员将开发用于治疗高级肉瘤患者的免疫治疗方法。在不久的将来，候选人旨在通过执行本提案中概述的研究来获得翻译研究人员的经验。这项工作的核心，候选人将作为阶段试验的PI，研究了自体NY-ESO-ESO-1特异性CD8+ T细胞用于患有晚期NY-ESO-1表达肉瘤的患者，该患者在一种新型调理方案的背景下，融合了IFNγ。这是候选人为临床前基础所写，设计和发展的大部分试验。通过作为此试验的PI，候选人将获得进行适应性免疫疗法试验的经验，并从该试验中获得收集和分析数据的经验。此外，该试验将作为启动多个基于实验室的转化研究的平台，调查针对该试验的患者免疫扫描机制，以及改善继任者试验的策略。该试验将在弗雷德·哈钦森癌症研究中心（Fred Hutchinson Cancer Research Center）进行，这是临床和转化研究的理想环境，是T细胞免疫疗法试验领域的领导者。斯坦利·里德尔（Stanley Riddell）博士是国际知名的癌症免疫学和适应性T细胞疗法试验的专家，他也是一种经验和成功的心态，将是心态的主要思维。候选人还召集了一个精神团队，由高级教师组成，每个教师都在其特定研究领域拥有国际知名的专业知识：Robin Jones（Robin Jones（专业知识）肉瘤临床护理和临床试验），马丁（MAC）Cheever（实体瘤免疫疗法试验的专业知识）和Cassian YEE（抗原特异性T细胞疗法试验的专业知识）。该提案的具体目的如下：目标1：在I期试验中进行评估，自体ny-Eso-1特异性CD8+细胞的毒性，持久性和抗肿瘤活性，该细胞用新型的调理方案，对IFNγ，环磷酰胺（CYCLophophamide（CY）和低剂量IL-2患者对患有高级MRCL和SSS的低剂量IL-2。目的2：评估抗原损失变体的出现和策略，以扩大接受适应性T细胞疗法的SS和MRCL患者的抗原性和抗原性。 AIM 3：评估将NY-ESO-1特异性CD4+ T细胞分离以增强或维持CD8+ T细胞功能的策略。