Oft M.,ARMO BioSciences
Blood | Year: 2013
In this issue of Blood, Neven et al report that a third of the patients with interleukin-10 receptor (IL-10R) deficiency develop B-cell lymphomas in the first decade of their life. The lymphomas uniformly contained amplifications of c-rel, activation of inflammatory nuclear factor kB (NF-kB) target genes, and a defective intratumoral CD81 T-cell tumor immunosurveillance. © 2013 by The American Society of Hematology.
Oft M.,ARMO BioSciences
Cancer immunology research | Year: 2014
Human cancer is characterized by deficits in antigen-specific immunity and intratumoral CD8(+) T cells. On the other hand, inflammatory macrophages and mediators of chronic inflammation are highly prevalent in patients with late-stage cancer. Intratumoral T-cell deficiency and chronic inflammation have been linked independently to a poor prognosis in patients with cancer, and therapeutic approaches to overcome either pathology separately are in clinical testing. The anti-inflammatory cytokine interleukin (IL)-10 suppresses macrophage and proinflammatory Th17 T-cell responses by inhibiting the inflammatory cytokines IL-6 and IL-12/23. Corroborating the anti-inflammatory action of IL-10, deficiency in IL-10 leads to a stimulation of inflammatory responses and inflammatory bowel disease. The anti-inflammatory role of IL-10 fostered the assumption that IL-10 undermines the immune response to cancer. However, mice and humans deficient in IL-10 signaling develop tumors spontaneously and at high rates. Overexpression of IL-10 in models of human cancer or treatment with a pegylated IL-10 (PEG-IL-10) led to tumor rejection and long-lasting tumor immunity. IL-10 stimulates cytotoxicity of CD8(+) T cells and the expression of IFN-γ in CD8(+) T cells. IL-10-induced tumor rejections are dependent on the expression of IFN-γ and granzymes in tumor-resident CD8(+) T cells and the upregulation of MHC molecules. These findings reconcile earlier clinical data, which showed that recombinant IL-10 increased IFN-γ and granzymes in the blood of treated individuals. PEG-IL-10 is therefore a unique therapeutic agent, which simultaneously stimulates antitumor immunity and inhibits tumor-associated inflammation. ©2014 AACR.
ARMO BioSciences | Date: 2016-05-26
Methods of modulating immune responses in subjects having oncology- and immune-related diseases, disorders and conditions by the administration of an IL-10 agent, including pegylated IL-10.
ARMO BioSciences | Date: 2015-01-09
Methods for determining dosing parameters associated with subcutaneous administration of IL-10 useful for the treatment and/or prevention of a cholesterol-related disease, disorder or condition, and pharmaceutical compositions associated therewith, are provided herein. Certain embodiments are directed to means for establishing a therapeutic range of an IL-10 agent in a subject. In some embodiments, particular parameters (e.g., hematological parameters) are monitored to provide an indication of the upper limit of the therapeutic range such that any untoward adverse effects are avoided.
ARMO BioSciences | Date: 2014-09-16
The present invention relates to the use of a peptide, or derivative thereof of general formula X_(1)X_(2)X_(3)-Thr-X_(4)-Lys-X_(5)-Arg-X_(6 )for promoting accelerated wound healing with reduced scarring. X_(1 )is Ala or Gly; X_(2 )is Tyr or Phe; X_(3), X_(4 )and X_(5 )are independently selected from the group comprising Met, Ile, Leu and Val; and X_(6 )is selected from the group comprising Asp, Gln and Glu.
ARMO BioSciences | Date: 2014-04-15
Methods of treating subjects having a disease or disorder responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.
ARMO BioSciences | Date: 2014-08-26
Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided, More particularly, the present disclosure relates to optimized dosing parameters to achieve and maintain efficacy in the treatment and/or prevention of metabolic diseases, disorders and conditions in a subject, while minimizing the adverse effects associated therewith. Particular embodiments are directed to the treatment and/or prevention of abnormally high levels of cholesterol and/or manifestation(s) of hypercholesterolemia in as subject.
ARMO BioSciences | Date: 2014-11-07
Methods of treating subjects having diseases, disorders, or conditions, including cancer and immune- and inflammatory-related disorders, via the administration of IL-10 in combination with one or more additional agents, and methods and models associated therewith, are provided.
ARMO BioSciences | Date: 2014-04-23
Interleukin-10 muteins and other interleukin-10-related molecules are described, as well as methods of identifying interleukin-10 muteins and other interleukin-10-related molecules. Also described herein are modifications of the foregoing, which modifications may enhance a property (e.g., half-life) of the muteins or other molecules compared to human interleukin-10. Particular interleukin-10 muteins and related molecules have comparable immunogenicity to human interleukin-10 and/or bioactivity at least comparable to human interleukin-10. Pharmaceutical compositions and methods of use are also described herein.
ARMO BioSciences | Date: 2014-06-13
The present invention relates to methods and other technologies that may be used to determine whether compositions (e.g., pharmaceutical compositions) comprising interleukin-10 molecules (e.g., pegylated interleukin-10) meet particular product-related specifications prior to being administered to a subject for the treatment and/or prevention of the diseases, disorders and conditions, and/or the symptoms thereof, described herein.