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

基本信息

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
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/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

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-?), 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，新型冠状病毒 SARS-CoV-2 或 COVID-19 已感染超过 100 万人，造成约 6.3 万人死亡（日期：2020 年 4 月 30 日）。虽然人们对这种冠状病毒知之甚少，但已知 COVID-19 会引发以铁蛋白和 d-二聚体升高为特征的病理性炎症，以及白细胞介素 (IL) -2R、6、10 和肿瘤坏死因子-α (TNF-α) 等促炎细胞因子。？），表明死亡可能是由于过度炎症导致的器官衰竭所致。根据我们休斯顿卫理公会医院 (HMH) 的观察结果以及一份针对中国武汉患者的报告，感染 COVID-19 的癌症患者出现重症并需要住院治疗的风险增加约 3.5 倍。本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，该治疗干预已获得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 Francisco, CA); 2- 应用单一供体储存的骨髓间充质干细胞 (MSC) 治疗 SARS-CoV-2 引起的急性呼吸衰竭的试点研究。我们建议在抗 IL6 受体托珠单抗抗体或 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资格和临床结果。我们的团队拥有独特的优势来开展这项研究，因为我们可以获得来自 COVID-19 癌症和非癌症（对照）患者的 1000 多个血液样本（血浆和血沉棕黄层细胞）样本。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有关的持续过程，以及疾病的管理如何影响这种反应，并最终帮助开发针对感染了 COVID-19 的癌症患者的免疫疗法。