Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy.

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

Validation of Procedures for Monitoring Crewmember Immune Function - Short Duration Biological Investigation

Validation of Procedures for Monitoring Crew Member Immune Function - Short Duration Biological Investigation (Integrated Immune-SDBI) will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flightcompatible immune monitoring strategy. Immune system changes will be monitored by collecting and analyzing blood, urine and saliva samples from crewmembers before, during and after space flight

Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

EBV (Epstein-Barr Virus) and other human DNA viruses are associated with autoimmune syndromes in epidemiologic studies. In this work, immunoglobulin G response to EBV-encoded proteins which share regions with human immune response proteins from the human host including ZEBRA (BZLF-1 encoded protein), BALF-2 recombinase expressed primarily during the viral lytic replication cycle, and EBNA-1 (Epstein-Barr Virus Nuclear Antigen) expressed during the viral latency cycle respectively were characterized using a laser-printed micro-array ( PEPperprint.com ). IgG response to conserved "A/T hooks" in EBV-encoded proteins such as EBNA-1 and the BALF-2 recombinase related to host DNA-binding proteins including RAG-1 recombinase and histones, and EBV-encoded virokines such as the IL-10 homologue BCRF-1 suggest further directions for clinical research. The author suggests that proteomic "molecular fingerprints" of the immune response to viral proteins shared with human immune response genes are potentially useful in early diagnosis and monitoring of autoantibody production and response to therapy in EBV-related autoimmune syndromes

A Novel Non-invasive Method to Detect RELM Beta Transcript in Gut Barrier Related Changes During a Gastrointestinal Nematode Infection

Currently, methods for monitoring changes of gut barrier integrity and the associated immune response via non-invasive means are limited. Therefore, we aimed to develop a novel non-invasive technique to investigate immunological host responses representing gut barrier changes in response to infection. We identified the mucous layer on feces from mice to be mainly composed of exfoliated intestinal epithelial cells. Expression of RELM-β, a gene prominently expressed in intestinal nematode infections, was used as an indicator of intestinal cellular barrier changes to infection. RELM-β was detected as early as 6 days post-infection (dpi) in exfoliated epithelial cells. Interestingly, RELM-β expression also mirrored the quality of the immune response, with higher amounts being detectable in a secondary infection and in high dose nematode infection in laboratory mice. This technique was also applicable to captured worm-infected wild house mice. We have therefore developed a novel non-invasive method reflecting gut barrier changes associated with alterations in cellular responses to a gastrointestinal nematode infection

Increasing Endurance of an Autonomous Robot using an Immune-Inspired Framework

This paper describes the implementation of an online immune-inspired framework to help increase endurance of an autonomous robot. Endurance is defined as the ability of the robot to exert itself for a long period of time. The immune-inspired framework provides such capability by monitoring the behavior of the robot to ensure continuous and safe behavior. The immune-inspired framework combines innate and adaptive immune inspired algorithms. Innate uses a dendritic cell based innate immune algorithm, and adaptive uses an instance based B-cell approach. Results presented in this paper shows that when the robot is implemented with the immune-inspired framework, health and survivability of a robot is improved, therefore increasing its endurance

The Serumal Concentration of Hbsag in Patiets with Chb/hiv Co-infection Comparing with Chb Mono-infection in the Different Phases of Natural Course of Chronic Hepatitis В

The prevalence and inclination to chronization of viral hepatitis B is 3 – 5 times higher in patients with HIV-infection than in HIV-negative ones. The natural clinical course of chronic hepatitis B (CHB) in patients with HIV has the features, connected with immune suppression and mutual influence of viruses. The quantitative determination of HBsAg allows the more precise monitoring of the natural course and the dynamics of treatment of patients with CHB but these features are little studied in patients with co-infection CHB/HIV. In the work was presented the comparative analysis of the results of quantitative determination of the serumal HBsAg in 59 Patients with co-infection CHB/HIV and 60 ones with chronic hepatitis. At the study it was established, that in patients with CHB/HIV co-infection were observed the reliably higher qHBsAg levels than in HIV-negative ones both in whole and in each CHB phase that depends on the immune suppression degree and DNA level of hepatitis B virus

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly

Adaptive and Online Health Monitoring System for Autonomous Aircraft

Good situation awareness is one of the key attributes required to maintain safe flight, especially for an Unmanned Aerial System (UAS). Good situation awareness can be achieved by incorporating an Adaptive Health Monitoring System (AHMS) to the aircraft. The AHMS monitors the flight outcome or flight behaviours of the aircraft based on its external environmental conditions and the behaviour of its internal systems. The AHMS does this by associating a health value to the aircraft's behaviour based on the progression of its sensory values produced by the aircraft's modules, components and/or subsystems. The AHMS indicates erroneous flight behaviour when a deviation to this health information is produced. This will be useful for a UAS because the pilot is taken out of the control loop and is unaware of how the environment and/or faults are affecting the behaviour of the aircraft. The autonomous pilot can use this health information to help produce safer and securer flight behaviour or fault tolerance to the aircraft. This allows the aircraft to fly safely in whatever the environmental conditions. This health information can also be used to help increase the endurance of the aircraft. This paper describes how the AHMS performs its capabilities