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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.

新型冠状病毒SARS-CoV-2或COVID-19仅在美国就感染了100多万人，死亡人数约为6.3万人（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会引发病理性炎症，其特征是铁蛋白和d-二聚体升高，以及促炎细胞因子如白细胞介素(IL) -2R、6、10和肿瘤坏死因子- α （TNF-Į）升高，这表明死亡可能是由于过度炎症导致的器官衰竭。根据我们在休斯顿卫理公会医院（HMH）和一份已发表的关于中国武汉患者的报告所观察到的，感染COVID-19的癌症患者发展为重症和需要住院治疗的风险增加了约3.5倍。该行政补充旨在深入了解在HMH接受试点治疗干预的癌症与非癌症COVID-19患者的免疫反应，这些患者已经获得了非常积极的临床结果：1-使用抗il -6受体抗体tocilizumab (Actemra, Genentech, South San Francisco， CA)；2-应用单一供体骨髓间充质基质细胞（MSC）治疗SARS-CoV-2诱导的急性呼吸衰竭的试点研究。我们建议在抗il - 6受体tocilizumab抗体或MSC治疗后确定COVID-19感染患者的炎症相关标志物和细胞因子谱，并建立相关的免疫谱来预测患者的资格和临床结果。我们的团队在开展这项研究方面具有独特的优势，因为我们可以获得来自COVID-19癌症和非癌症（对照）患者的一千多份血液样本（血浆和黄皮细胞）。我们相信这将有助于了解受病毒感染的癌症患者的免疫反应相关的持续过程，以及疾病管理如何影响这种反应，并最终有助于开发COVID-19感染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.