Research Specialist Support of a Well-Established Cancer Immunotherapy Research Program Focused on Improving Adoptive T Cell Therapy (ACT)

研究专家支持完善的癌症免疫治疗研究计划，重点是改善过继性 T 细胞治疗 (ACT)

• 批准号: 10188114
• 负责人: Megan M Wyatt
• 金额: $ 10.81万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-10 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188114
• 关键词: Adoptive Immunotherapy; Award; Biopsy; CD28 gene; CD4 Positive T Lymphocytes; CRISPR/Cas technology; Cancer Center; Cancer Patient; Cells; Collaborations; Dipeptidyl Peptidases; Dipeptidyl-Peptidase IV; Doctor of Philosophy; Enzymes; Exhibits; Future; Generations; Goals; Grant; Human; Immunology; Immunotherapy; Interleukin-2; Knock-out; Laboratories; Learning; Master of Science; Medical; Memory; Microbiology; Pathway interactions; Physicians; Property; Protocols documentation; Publications; Research; Research Personnel; Role; Running; Scientist; South Carolina; Specialist; T cell therapy; T-Lymphocyte; Training; Translational Research; Tumor Immunity; Universities; Work; cancer immunotherapy; career; cellular transduction; clinically significant; college; experimental study; improved; in vivo; interest; long term memory; programs; skills; stemness; success; tumor

Project Summary Megan Wyatt, MS is a senior Research Specialist in Chrystal Paulos, Ph.D.’s laboratory at the Medical University of South Carolina’s Hollings Cancer Center in the department of Microbiology and Immunology. Dr. Paulos is a well-established cancer immunotherapy researcher, with two current NCI R01 awards, to which Ms. Wyatt has made significant contributions. The first R01 focuses on the inducible costimulator (ICOS), which endows Th17 cells with a superior tumor-killing ability compared to those stimulated with CD28. This R01 aims to determine the mechanism by which ICOS co-stimulation promotes long-term memory and antitumor activity of Th17 cells, by focusing on a core of distinct pathways that may support their persistence, antitumor activity and durable memory generation. The second R01 builds off the Paulos lab’s discovery that human CD4+ T cell which express high levels of the enzyme dipeptidyl peptidase 4 (DPP4), also known as CD26, exhibit superior antitumor activity compared to the traditional Th1, Th2, and even Th17 subsets. The goal of this R01 is to identify the mechanisms by which CD26 regulates the antitumor activity of CD26high CD4+ T cells in vivo, and to clarify the stemness properties of these cells. Ms. Wyatt developed an interest in translational research while completing her Master of Science degree at the College of Charleston. She joined Dr. Paulos’ lab after learning of her exciting immunotherapy research. Ms. Wyatt was first assigned to run a P01-derived T cell transduction core, which developed her basic T cell research skills and allowed her to contribute to several different projects with the labs within the P01 grant. Her efforts on this project has been featured in several high-impact publications from both Dr. Paulos’ group and other co-investigators. Ms. Wyatt became quite proficient in T cell transduction because of her work in the core, and has been sought out for her expertise by other researchers both at MUSC and externally looking for training and assistance in developing their own transduction protocols. As the P01 ended, Dr. Paulos transitioned Ms. Wyatt to various projects supporting her two R01 grants. Ms. Wyatt has taken on the role of processing and analyzing tumor biopsies obtained from Dr. Paulos’ collaborations with physician scientists at MUSC, and using findings from these studies to further the clinical significance of Dr. Paulos’ research programs. She also successfully brought CRISPR/Cas9 technology into the lab and was able to knock out CD26 from human T cells, allowing for further exploration into its role in antitumor immunity. Moving forward, Ms. Wyatt will continue to support Dr. Paulos’ research programs by conducting critical experiments for the CD26 R01, and providing assistance and guidance for the continuation of the ICOS R01. Her efforts will be essential to the success of these programs, and will be critical for Dr. Paulos to further develop new research programs which will continue to advance and improve adoptive immunotherapy for cancer patients.

项目概要 梅根·怀亚特 (Megan Wyatt) 理学硕士是医学院 Chrystal Paulos 博士实验室的高级研究专家 南卡罗来纳大学霍林斯癌症中心微生物学和免疫学系。博士。 Paulos 是一位知名的癌症免疫治疗研究人员，目前荣获两项 NCI R01 奖项。 怀亚特做出了重大贡献。第一个 R01 专注于诱导共刺激器 (ICOS)， 与 CD28 刺激的细胞相比，Th17 细胞具有更强的肿瘤杀伤能力。这款 R01 的目标 确定 ICOS 共刺激促进长期记忆和抗肿瘤活性的机制 Th17 细胞，通过关注可能支持其持久性、抗肿瘤活性的不同途径的核心 和持久的记忆生成。第二个 R01 以 Paulos 实验室的发现为基础，即人类 CD4+ T 细胞 表达高水平的二肽基肽酶 4 (DPP4)（也称为 CD26），表现出优越的性能 与传统的 Th1、Th2 甚至 Th17 亚群相比，其抗肿瘤活性更高。 R01 的目标是 确定 CD26 在体内调节 CD26high CD4+ T 细胞抗肿瘤活性的机制，并 阐明这些细胞的干性特性。 怀亚特女士在完成她的理学硕士学位时对转化研究产生了兴趣 查尔斯顿学院。在了解了 Paulos 博士令人兴奋的免疫治疗研究后，她加入了他的实验室。多发性硬化症。 Wyatt 首先被指派运行 P01 衍生的 T 细胞转导核心，该核心开发了她的基础 T 细胞 研究技能，并让她能够在 P01 拨款范围内为实验室的几个不同项目做出贡献。她 Paulos 博士的团队和一些具有高影响力的出版物中都介绍了该项目的努力 其他共同研究者。 Wyatt 女士由于在 T 细胞转导方面的工作而变得相当精通。 MUSC 的其他研究人员和外部寻找人员都在寻找她的专业知识 制定自己的转导协议方面的培训和协助。随着 P01 的结束，Paulos 博士 将 Wyatt 女士转入各种项目，支持她的两笔 R01 赠款。怀亚特女士担任的角色 处理和分析 Paulos 博士与医学科学家合作获得的肿瘤活检样本 MUSC，并利用这些研究结果进一步增强 Paulos 博士研究的临床意义 程序。她还成功地将CRISPR/Cas9技术带入实验室，并能够敲除 来自人类 T 细胞的 CD26，可以进一步探索其在抗肿瘤免疫中的作用。继续前进， 怀亚特女士将继续支持保罗博士的研究项目，为 CD26 R01，并为 ICOS R01 的延续提供帮助和指导。她的努力将会是 这些项目的成功至关重要，对于 Paulos 博士进一步开展新研究也至关重要 将继续推进和改进癌症患者过继免疫治疗的计划。