Targeted Therapy for Leukemia

白血病靶向治疗

• 批准号: 10251287
• 负责人: JOHN C. BYRD
• 金额: $ 97.12万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251287
• 关键词: Animal Model; Area; Biological; Chronic Lymphocytic Leukemia; Collaborations; Data; Disease; Disease model; Disease remission; Drug Delivery Systems; Genetic; Genetic study; Hematologic Neoplasms; Hematopoietic Neoplasms; Immune Tolerance; Immunotherapy; Investigation; Knowledge; Laboratories; Laboratory Research; Methods; Pathway interactions; Patients; Primary Neoplasm; Proteomics; Research; Research Personnel; Sampling; Techniques; Translating; Work; adult leukemia; clinical application; clinically relevant; curative treatments; human disease; immunoregulation; leukemia; mouse model; next generation sequencing; novel; novel therapeutics; programs; public health relevance; recruit; targeted treatment; therapeutic development; therapeutic target; tumor

 DESCRIPTION (provided by applicant): The Byrd translational laboratory research program focuses on basic and translational biologic questions to develop novel immunologic and targeted therapies for hematologic malignancies. Chronic lymphocytic leukemia (CLL) is utilized as our disease model as it allows integration of mechanistic and genetic studies in spontaneous leukemia mouse models with studies using primary tumor samples, thereby enhancing the clinical relevance of our findings. Our highly collaborative laboratory team works to identify, dissect, and solve challenges in leukemia therapeutic development that capitalizes on the strengths of each to drive projects to clinical application. It also allows us to exploit diverse techniques (e.g. proteomics, next-generation sequencing) and embark on new areas (e.g. novel drug delivery methods, target identification, introduction of new animal models) to translate our findings across multiple human diseases. This strategy has resulted in powerful collaborations, recruiting skilled researchers from other fields to apply their knowledge to leukemia. I envision the greatest impact from my research will come from integrating therapeutics that target tumor survival pathways with agents that reverse immune tolerance to facilitate long-term remissions or cure. My work to date has resulted in the approval of two agents for CLL therapy that prolong survival. Our ongoing work with imbrutinib dispels a commonly held paradigm that it is not possible to develop a general "disease-targeted therapy" when a specific genetic aberration is not present. My hypothesis is that general disease-targeted therapy requires dual tumor-targeted and immunologic modulation. I seek to aggressively develop this concept and extend it to other areas as our data directs us.

 描述（由应用程序提供）：BYRD转化实验室研究计划的重点是基本和翻译的生物学问题，以开发新型的免疫学和靶向靶向疗法，用于血液学恶性肿瘤。慢性淋巴细胞性白血病（CLL）被用作我们的疾病模型，因为它允许在赞助性白血病小鼠模型中与使用原发性肿瘤样本的研究整合机械和遗传研究，从而增强了我们发现的临床相关性。我们高度合作的实验室团队致力于识别，剖析和解决白血病理论开发中的挑战，这些挑战利用了每个人的优势，以将项目推向临床应用。它还使我们能够利用潜水员技术（例如蛋白质组学，下一代测序），并启动新领域（例如，新型药物输送方法，靶标识别，新动物模型的引入），以转化跨多种人类疾病的发现。该策略导致了强大的合作，从其他领域招募了熟练的研究人员将其知识应用于白血病。我认为，我的研究产生的最大影响将来自整合疗法，该治疗将肿瘤存活途径与逆转免疫耐受力的药物靶向以促进长期恢复或治愈。迄今为止，我的工作已批准了两种延长生存率的CLL治疗的药物。我们正在进行的与Imbrutinib的合作消除了一个普遍认为的范式，即当不存在特定的遗传像差时，不可能开发一般的“靶向疾病靶向疗法”。我的假设是，以疾病为目标的一般疗法需要以双重肿瘤为目标和免疫学调节。我试图积极地发展这一概念，并在我们的数据指示我们时将其扩展到其他领域。

项目成果

Characterization and mitigation of fragmentation enzyme-induced dual stranded artifacts.

• DOI: 10.1093/nargab/lqaa070
• 发表时间: 2020-12
• 期刊: NAR genomics and bioinformatics
• 影响因子: 4.6
• 作者: Gregory T;Ngankeu A;Orwick S;Kautto EA;Woyach JA;Byrd JC;Blachly JS
• 通讯作者: Blachly JS

Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients.

• DOI: 10.3324/haematol.2021.278901
• 发表时间: 2022-06-01
• 期刊: HAEMATOLOGICA
• 影响因子: 10.1
• 作者: Brown, Jennifer R.;Byrd, John C.;Ghia, Paolo;Sharman, Jeff P.;Hillmen, Peter;Stephens, Deborah M.;Sun, Clare;Jurczak, Wojciech;Pagel, John M.;Ferrajoli, Alessandra;Patel, Priti;Tao, Lin;Kuptsova-Clarkson, Nataliya;Moslehi, Javid;Furman, Richard R.
• 通讯作者: Furman, Richard R.

Lenalidomide Induces Interleukin-21 Production by T Cells and Enhances IL21-Mediated Cytotoxicity in Chronic Lymphocytic Leukemia B Cells.

• DOI: 10.1158/2326-6066.cir-15-0291
• 发表时间: 2016-08
• 期刊: Cancer immunology research
• 影响因子: 10.1
• 作者: Browning RL;Byrd WH;Gupta N;Jones J;Mo X;Hertlein E;Yu L;Muthusamy N;Byrd JC
• 通讯作者: Byrd JC

Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial.

• DOI: 10.1200/jco.21.01210
• 发表时间: 2021-11-01
• 期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• 作者: Byrd JC;Hillmen P;Ghia P;Kater AP;Chanan-Khan A;Furman RR;O'Brien S;Yenerel MN;Illés A;Kay N;Garcia-Marco JA;Mato A;Pinilla-Ibarz J;Seymour JF;Lepretre S;Stilgenbauer S;Robak T;Rothbaum W;Izumi R;Hamdy A;Patel P;Higgins K;Sohoni S;Jurczak W
• 通讯作者: Jurczak W

Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials.

• DOI: 10.3324/haematol.2017.171041
• 发表时间: 2017-10
• 期刊: Haematologica
• 影响因子: 10.1
• 作者: Brown JR;Moslehi J;O'Brien S;Ghia P;Hillmen P;Cymbalista F;Shanafelt TD;Fraser G;Rule S;Kipps TJ;Coutre S;Dilhuydy MS;Cramer P;Tedeschi A;Jaeger U;Dreyling M;Byrd JC;Howes A;Todd M;Vermeulen J;James DF;Clow F;Styles L;Valentino R;Wildgust M;Mahler M;Burger JA
• 通讯作者: Burger JA