Targeting the Inflammasome As a Treatment Strategy for COVID-19 infected cancer patients

以炎症小体为目标作为治疗 COVID-19 感染癌症患者的策略

基本信息

批准号：
10161460
负责人：
JENNY C-N CHANG
金额：
$ 16.15万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-29 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10161460
关键词：
2019-nCoV Acute respiratory failure Address Administrative Supplement Affect Age Antibodies B-Lymphocytes Biological Markers Biological Response Modifiers Biomimetics Blood Cells Blood specimen Bone Banks Bone Marrow COVID-19 Cancer Patient Cells Cessation of life Characteristics China Clinical Control Groups Coronavirus Data Development Disease Disease Management Eligibility Determination Expression Profiling Fc Receptor Ferritin Fibrin fragment D Gene Expression Gene Expression Profiling Glycocalyx Goals Grant Hospitalization Hospitals Hour Immune Immune response Immunity Immunocompromised Host Immunologic Tests Immunotherapeutic agent Immunotherapy Infection Inflammasome Inflammation Inflammatory Interleukin 6 Receptor Interleukin-6 Interleukins Investigation Knowledge Length Malignant Neoplasms Malignant neoplasm of lung Mesenchymal Stem Cells Methodist Church Myeloid Cells Organ failure Outcome Pathologic Patients Peripheral Blood Mononuclear Cell Pilot Projects Plasma Plasma Cells Population Process Protocols documentation Publishing RNA Reporting Risk Sampling San Francisco Severities Signal Pathway Systemic Inflammatory Response Syndrome T-Lymphocyte TNF gene Techniques Testing Therapeutic Therapeutic Intervention Time Treatment Protocols United States Vaccines Ventilator Virus Virus Diseases age group care outcomes cell type comorbidity cytokine cytokine release syndrome design effective therapy granulocyte high risk high risk population immunomodulatory therapies inhibitor/antagonist insight macrophage mesenchymal stromal cell mortality nanotherapeutic novel coronavirus novel therapeutics pandemic disease patient population research clinical testing response statistics transcriptome sequencing treatment strategy working group

项目摘要

The novel coronavirus SARS-CoV-2 or COVID-19 has infected over a million people with approximately 63K deaths in the United States alone (date: April 30, 2020). While little is known about this coronavirus, COVID-19 is known to initiate pathologic inflammation characterized by elevated ferritin and d-dimer, and proinflammatory cytokines such as interleukin (IL) -2R, 6, 10 and Tumor Necrosis Factor-alpha (TNF-Į), suggesting that mortality might be due to organ failure driven by hyperinflammation. Cancer patients with COVID-19 infection are at about 3.5 times increased risk of developing severe cases and requiring hospitalization, as has been observed at our Houston Methodist Hospital (HMH) and a published report on patients in Wuhan, China. This administrative supplement is designed to gain in-depth insights onto the immune response of cancer vs. non-cancer COVID-19 patients undergoing pilot therapeutic interventions at HMH that has received very positive clinical outcomes: 1- the use of tocilizumab, an anti-IL-6 receptor antibody (Actemra, Genentech, South San Francisco, CA); and 2- a pilot study of applying Single Donor Banked Bone Marrow Mesenchymal Stromal Cells (MSC) for the Treatment of SARS-CoV-2 Induced Acute Respiratory Failure. We propose to determine the inflammation-related markers and cytokine profiles in COVID-19 infected patients following either anti-IL6 receptor tocilizumab antibody or MSC treatments and to establish correlative immune profiles to predict patient eligibility and clinical outcome. Our group is uniquely poised to conduct this study as we have access to more than a thousand samples of blood specimens (plasma and buffy coat cells) from COVID-19 cancer and non-cancer (control) patients. We believe this will help understand the ongoing processes related to both the immunological response in cancer patients affected with the viral infection and how the management of the disease affect that response and ultimately help develop immunotherapies in COVID-19 infected cancer patients.

仅在美国，冠状病毒SARS-COV-2或COVID-19，就感染了超过100万人死亡的人（日期：2020年4月30日）。虽然对这种冠状病毒知之甚少，但已知Covid-19引发病理炎症，其特征是铁蛋白和D-二聚体升高，以及促炎细胞因子（例如白介素（IL）-2R，6、10和肿瘤坏死因子 - α-Alpha（TNF-į），表明是由Ortyflative Ortander drived driven factive hyperfly driven factive hypersive diverflative hypersive tyfly factive tyfly Fllicative hypersive Ortander diver tyfly frol throffer factive Ortance Ortander diverfflin。正如我们的休斯顿卫理公会医院（HMH）所观察到的那样，患有COVID-19感染的癌症患者的风险增加了约3.5倍，并需要住院治疗，并且在中国武汉发表了有关患者的报告。该管理补充剂旨在获得对癌症免疫反应的深入见解。在HMH处进行试验治疗干预措施的非癌症Covid-19患者接受了非常积极的临床结果：1-使用抗IL-6受体抗体Tocilizumab的使用（Actemra，Actemra，Genentech，South San San Francisco，CA）； 2-一项针对应用单个供体的骨髓间充质基质细胞（MSC）的试验研究，以治疗SARS-COV-2诱导的急性呼吸衰竭。我们建议在抗IL6受体tocilizumab抗体或MSC治疗后确定Covid-19受感染患者的炎症相关标记和细胞因子谱，并建立相关免疫特征以预测患者的可用性和临床结果。我们的小组被毒死以进行这项研究，因为我们可以从Covid-19癌症和非癌症（对照）患者中获得超过一千种的血液样本（等离子体和Buffy Coat细胞）。我们认为，这将有助于了解与受病毒感染影响的癌症患者的免疫反应有关的持续过程，以及疾病的管理如何影响该反应并最终有助于发展Covid-19受感染的癌症患者的免疫疗法。

项目成果

期刊论文数量（34）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Extension of a multiphase tumour growth model to study nanoparticle delivery to solid tumours.

扩展多相肿瘤生长模型以研究纳米颗粒向实体瘤的递送。

DOI：
10.1371/journal.pone.0228443
发表时间：
2020
期刊：
PloS one
影响因子：
3.7
作者：
Wirthl,Barbara;Kremheller,Johannes;Schrefler,BernhardA;Wall,WolfgangA
通讯作者：
Wall,WolfgangA

Predictive Modeling for Voxel-Based Quantification of Imaging-Based Subtypes of Pancreatic Ductal Adenocarcinoma (PDAC): A Multi-Institutional Study.

DOI：
10.3390/cancers12123656
发表时间：
2020-12-05
期刊：
Cancers
影响因子：
5.2
作者：
Zaid M;Widmann L;Dai A;Sun K;Zhang J;Zhao J;Hurd MW;Varadhachary GR;Wolff RA;Maitra A;Katz MHG;Herman JM;Wang H;Knopp MV;Williams TM;Bhosale P;Tamm EP;Koay EJ
通讯作者：
Koay EJ

Immunotherapeutic Transport Oncophysics: Space, Time, and Immune Activation in Cancer.