Researchers led by Bernard Vanove of OSE Immunotherapeutics report in the December 7, 2016 issue of the Journal of Immunology on the first-in-human study of FR1041. OSE and collaborators at the University of Nantes and Janssen conducted a detailed phase I evaluation of safety, pharmacokinetics, pharmacodynamics and potency of FR104 in healthy volunteers.
More commonly known as an inhibitory cytokine, high doses of interleukin 10 (IL-10) have been shown to lead to the activation and survival of antigen stimulated CD8 T cells. According to a study published in the Journal of Clinical Oncology, the investigators in this first-in-human, phase 1 clinical trial of IL-10 (AM0010), demonstrate antitumor activity and therapy tolerability in a pretreated population. The primary endpoint of the study was to establish safety, tolerability and the maximum tolerated dose. This goal appears to have been met, with a low incidence of adverse events, most of which were temporary or reversible. The dose-escalation study was followed by a renal cell cancer dose-expansion cohort.
Published in the September 6, 2016 issue of Cell Reports, Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses describes the use of the Myriad RBM TruCulture® platform for standardized ex vivo immune stimulation and a high-throughput method for gene expression profiling to explore immune variance within a population.
VentiRx, the developers of motolimod, a TLR8 agonist, have published preclinical and clinical results that indicate effective immune system stimulation in human whole blood cultures, non-human primates, healthy subjects, and late-stage cancer patients. Immune system stimulation in all of these settings is dose-dependent, characterized by similar biomarkers, and consistent with stimulation via the TLR8 pathway. The rapid translation and development of motolimod clearly benefited from the use of standardized immune monitoring systems and validated biomarker assays.
New research published in Immunity describes a standardized method to reproducibly measure a functional immune response in healthy donors. Conducted by researchers at the Institut Pasteur, the study defines protein signatures of the healthy immune response to several relevant stimuli, including common pathogenic microorganisms, defined host sensor agonists, clinically employed cytokines, and activators of T-cell immunity. The research promises to help scientists understand and better predict immune response, in addition to informing therapeutic intervention. https://www.cell.com/immunity/abstract/S1074-7613(14)00081-8
Investigators observed samples from 84 naturally influenza-infected individuals and found increased levels of cytokines MCP-3, IFNa2 and plasma IL-10 predicted progression to more severe flu symptoms. While increased levels of plasma IL-10, MCP-3 and IL-6 levels predicted hospitalization. The findings from this paper also explain why infants are at high risk for complications, and why the benefits from antiviral drug oseltamivir are short-lived. https://www.atsjournals.org/doi/abs/10.1164/rccm.201309-1616OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&&&#%2EUwYwmmfnZ1P
In this paper, published in the Journal of Biological Chemistry, researchers used Myriad RBM’s services to discover a cytokine signature that was indicative of the in vitro PBMC response to aggregated biotherapeutics. These aggregates initiate immune system activation through specific cell surface receptors and a downstream T-cell response. Identifying a protein signature that describes a biotherapeutic immune response has great potential for helping determine the immunogenicity risk of these compounds.