Transport of Effector T cells and Nano-DC vaccine in Breast Cancer

效应 T 细胞和 Nano-DC 疫苗在乳腺癌中的运输

• 批准号: 10227174
• 负责人: Rongfu Wang
• 金额: $ 16.15万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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/10227174
• 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; effector T cell; granulocyte; high risk; high risk population; immunomodulatory therapies; inhibitor/antagonist; insight; macrophage; malignant breast neoplasm; mesenchymal stromal cell; mortality; nano; nanotherapeutic; novel coronavirus; novel therapeutics; pandemic disease; patient population; research clinical testing; response; statistics; transcriptome sequencing; treatment strategy; working group

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-?), 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仅在美国就感染了超过100万人，死亡人数约为63，000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，如白介素（IL）-2R，6，10和肿瘤坏死因子-α（TNF-？），这表明死亡可能是由于炎症过度导致的器官衰竭。正如我们休斯顿卫理公会医院（HMH）和中国武汉患者已发表的报告所观察到的那样，感染COVID-19的癌症患者出现重症病例和需要住院治疗的风险增加约3.5倍。本行政补充材料旨在深入了解在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，该干预措施已收到非常积极的临床结果：1-使用托珠单抗（一种抗IL-6）受体抗体（Actemra，Genentech，South San弗朗西斯科，CA）; 2.应用单个供体库骨髓间充质干细胞（MSC）治疗SARS-CoV-2诱导的急性呼吸衰竭的初步研究。我们建议确定COVID-19感染患者在抗IL-6受体托珠单抗抗体或MSC治疗后的炎症相关标志物和细胞因子谱，并建立相关的免疫谱以预测患者的资格和临床结果。我们的团队是唯一准备进行这项研究，因为我们有机会从COVID-19癌症和非癌症（对照）患者获得超过一千份血液标本（血浆和血沉棕黄层细胞）。我们相信，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相关的持续过程，以及疾病的管理如何影响这种反应，并最终帮助开发COVID-19感染癌症患者的免疫疗法。