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

项目摘要 梅根·怀亚特，医学硕士，克里斯特尔·保罗博士，S医学实验室高级研究专家 南卡罗来纳大学霍林斯癌症中心微生物学和免疫学系。Dr。 Paulos是一位享有盛誉的癌症免疫治疗研究员，目前获得了两项NCI R01奖。 怀亚特做出了重大贡献。第一个R01集中在可诱导共刺激分子(ICOS)上，它 与CD28刺激的Th17细胞相比，赋予Th17细胞更强的肿瘤杀伤能力。本R01的目标是 确定ICOS共刺激促进长时记忆和抗肿瘤活性的机制 Th17细胞，通过聚焦于可能支持其持久性、抗肿瘤活性的不同途径的核心 和耐久记忆生成。第二个R01建立在Paulos实验室发现的人类CD4T细胞 表达高水平的二肽基肽酶4(DPP4)，也被称为CD26，表现出优越的 抗肿瘤活性与传统的Th1、Th2、甚至Th17亚群相比。这款R01的目标是 鉴定CD26在体内调节CD26高CD4T细胞抗肿瘤活性的机制 阐明这些细胞的干性属性。 怀亚特女士在攻读理科硕士学位期间，对翻译研究产生了兴趣。 查尔斯顿大学。在得知她的令人兴奋的免疫疗法研究后，她加入了保罗博士的实验室。女士。 怀亚特首先被指派负责P01来源的T细胞转导核心，该核心形成了她的基本T细胞 研究技能，并允许她在P01拨款范围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被Paulos博士的小组和 其他合作调查员。怀亚特女士在T细胞转导方面变得相当熟练，因为她在 CORE，并一直被南加州大学的其他研究人员和外部寻找她的专业知识 在制定自己的转导方案方面提供培训和帮助。随着P01的结束，保罗博士 将怀亚特女士过渡到各种项目，以支持她的两笔R01赠款。怀亚特女士承担起了 处理和分析Paulos博士与内科科学家合作获得的肿瘤活检组织，网址为 并利用这些研究的结果来进一步说明Paulos博士的研究的临床意义 程序。她还成功地将CRISPR/Cas9技术引入实验室，并能够击倒 CD26从人T细胞中分离出来，为进一步探讨其在抗肿瘤免疫中的作用奠定了基础。往前看， 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。她的努力将是 对这些项目的成功至关重要，对Paulos博士进一步发展新的研究将是至关重要的 将继续推进和改进癌症患者过继免疫治疗的计划。

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.