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: 10242967
• 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/10242967
• 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.

项目摘要 Megan Wyatt，MS是Chrystal Paulos博士的高级研究专家。医学实验室 南卡罗来纳州大学微生物学和免疫学系的霍林斯癌症中心。博士 Paulos是一位知名的癌症免疫治疗研究人员，目前拥有两项NCI R 01奖项。 怀亚特做出了重大贡献。第一个R 01侧重于诱导型共刺激分子（ICOS）， 与用CD 28刺激的Th 17细胞相比，赋予Th 17细胞上级肿瘤杀伤能力。R 01旨在 确定ICOS共刺激促进长期记忆和抗肿瘤活性的机制 Th 17细胞，通过关注可能支持其持久性的不同途径的核心， 和持久的记忆生成。第二个R 01建立在Paulos实验室的发现基础上，即人类CD 4 + T细胞 其表达高水平的酶二肽基肽酶4（DPP 4），也称为CD 26，表现出上级 与传统的Th 1、Th 2甚至Th 17亚群相比，本R 01的目标是 确定CD 26在体内调节CD 26 high CD 4 + T细胞抗肿瘤活性的机制， 阐明这些细胞的干细胞特性。 女士Wyatt在完成理学硕士学位的同时，对翻译研究产生了兴趣。 查尔斯顿学院。在了解到Paulos博士令人兴奋的免疫疗法研究后，她加入了Paulos博士的实验室。女士 Wyatt首先被指派运行P01衍生的T细胞转导核心，这使她的基础T细胞 研究技能，并允许她在P01赠款内与实验室一起为几个不同的项目做出贡献。她 在这个项目上的努力已经在Paulos博士的小组和 其他研究人员。怀亚特女士变得相当精通T细胞转导，因为她在 核心，并已寻求她的专业知识，由其他研究人员都在MUSC和外部寻找 培训和协助制定自己的转导方案。随着P01的结束，Paulos博士 将怀亚特女士过渡到支持她的两个R 01赠款的各种项目。怀亚特女士担任了 处理和分析从Paulos博士与内科科学家合作中获得的肿瘤活检， MUSC，并利用这些研究的结果来进一步提高Paulos博士研究的临床意义 程序.她还成功将CRISPR/Cas9技术带入实验室并成功敲除 从人T细胞的CD 26，允许进一步探索其在抗肿瘤免疫中的作用。今后， 女士怀亚特将继续支持博士Paulos的研究计划，进行关键的实验， CD 26 R 01，并为ICOS R 01的继续提供援助和指导。她的努力将是 这对这些项目的成功至关重要，对Paulos博士进一步开发新的研究也至关重要。 这些计划将继续推进和改善癌症患者的过继免疫治疗。