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1.
Front Immunol ; 11: 2059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013871

RESUMO

The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Imunidade Inata , Memória Imunológica/imunologia , Pneumonia Viral/imunologia , Vacinação , Idoso , Animais , COVID-19 , Vacinas contra COVID-19 , Vacinas Anticâncer/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Humanos , Micobactérias não Tuberculosas/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Risco , SARS-CoV-2 , Vacinas Virais/efeitos adversos
2.
J Immunother Cancer ; 3: 46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26579224

RESUMO

A novel form of immune cell quantification in blood and tissue is described using epigenetic - based, quantitative real-time PCR assisted cell counting (qPACC). The methylation status of the chromatin structure of either actively expressed or silenced genes is the basis of the epigenetic-based cell identification and quantification technology. Discovery of cell type specific removal of methyl groups (demethylation) from the 5'-carbon of the cytosine base in the dinucleotide cytosine phosphate guanine permits precise and robust quantification of immune cells from only small amounts of human blood or tissue samples. These epigenetic biomarkers located on genomic DNA are stably associated with a cell type of interest.

3.
Clin Cancer Res ; 17(10): 3064-76, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21558394

RESUMO

PURPOSE: To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of antitumor immunity to measure and which assays are optimal for those measurements. EXPERIMENTAL DESIGN: The iSBTc-SITC (International Society for Biological Therapy of Cancer-Society for Immunotherapy of Cancer), FDA (Food and Drug Administration), and NCI (National Cancer Institute) partnered to address these issues for immunotherapy of cancer. Here, we review the major challenges, give examples of approaches and solutions, and present our recommendations. RESULTS AND CONCLUSIONS: Although specific immune parameters and assays are not yet validated, we recommend following standardized (accurate, precise, and reproducible) protocols and use of functional assays for the primary immunologic readouts of a trial; consideration of central laboratories for immune monitoring of large, multi-institutional trials; and standardized testing of several phenotypic and functional potential potency assays specific to any cellular product. When reporting results, the full QA (quality assessment)/QC (quality control) should be conducted and selected examples of truly representative raw data and assay performance characteristics should be included. Finally, to promote broader analysis of multiple aspects of immunity, and gather data on variability, we recommend that in addition to cells and serum, RNA and DNA samples be banked (under standardized conditions) for later testing. We also recommend that sufficient blood be drawn to allow for planned testing of the primary hypothesis being addressed in the trial, and that additional baseline and posttreatment blood is banked for testing novel hypotheses (or generating new hypotheses) that arise in the field.


Assuntos
Biomarcadores Tumorais/análise , Imunoterapia/métodos , Neoplasias/diagnóstico , Neoplasias/terapia , Guias de Prática Clínica como Assunto , Conferências de Consenso como Assunto , Diretrizes para o Planejamento em Saúde , Humanos , Imunoterapia/legislação & jurisprudência , Agências Internacionais/legislação & jurisprudência , Oncologia/legislação & jurisprudência , Oncologia/métodos , Oncologia/organização & administração , National Cancer Institute (U.S.)/legislação & jurisprudência , Sociedades Médicas/legislação & jurisprudência , Sociedades Médicas/organização & administração , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência
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