Merck Sharp + Dohme Corp.

Armo Biosciences, Inc.

Synthekine, Inc.

Schering Corporation

Eli Lilly and Company

Martin Oft

John Brian Mumm

Catherine Sheppard

Lingling Wu

Scott Alan McCauley

Steve Kauder

Terrill K McClanahan

Paul-Joseph Penaflor-Aspuria

Robert A Kastelein

J Fernando Bazan

Ivan Ho Chan

Scott Ogg

Jan Emmerich

Jochen Schmitz

Scott McCauley

John Mumm

Linling Wu

Wu Lingling

The present disclosure relates to hIL2 orthogonal ligands ('IL2 orthologs') that specifically and selectively bind to the extracellular domain (ECD) a transmembrane polypeptide comprising of a modified hCD122 polypeptide. The binding of the hIL2 ortholog to the modified hCD122 polypeptide participates in the transduction pathway of intracellular signaling resulting in a biological activity of the native intracellular signaling patterns associated with hIL2 binding to either the intermediate or high affinity hIL2 receptor but which exhibits selectivity to an engineered cell expressing an hCD122 orthogonal receptor. The hIL2 orthologs of the present invention exhibit significantly reduced binding relative to their binding to the extracellular domain of wild type hCD122, either alone or when hCD122 is present in the form of an endogenous high or intermediate affinity hIL2 receptors.

IL-2 orthologs and methods of use

The present disclosure provides methods and compositions relating to isolated CD8+ T cells expressing a disease antigen-specific T cell receptor, as well as nucleic acids encoding the V&#x3b1; and V&#x3b2; polypeptide pairs of T cell receptors (TCRs) of such disease antigen-specific T cells. Such disease antigen-specific CD8+ T cells are obtainable from the periphery (e.g., blood) of a subject having a disease amenable to treatment with an IL-10 agent. The present disclosure also contemplates therapeutic methods and compositions relating to administration of isolated disease antigen-specific CD8+ T cells to a subject, as well as therapeutic methods and compositions relating to CD8+ T cells genetically modified to express a disease antigen-specific TCR and/or chimeric antigen receptor.

Interleukin-10 production of antigen-specific CD8+ T cells and methods of use of same

The present disclosures related to human interleukin-2 (hIL2) muteins, pharmaceutical formulations thereof, methods for preparing interleukin-2 muteins, recombinant vectors and cells comprising nucleic acids encoding IL2 muteins and methods for the treatment of human disease.

Biased IL2 muteins methods and compositions

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.

Methods of using interleukin-10 for treating diseases and disorders

Methods of treating subjects having a disease or disorder responsive to IL-10, including methods of administration and dosing regimens associated therewith, are provided.

Methods of treating cancer metastasis by using interleukin-10

Provided are methods of treatment for tumors. In particular, methods are provided for use of a chemically modified IL-10 to treat tumors.

Methods for treatment of cancer with therapeutic combinations comprising PEG-IL-10

Methods of using interleukin-10 for treating solid tumors

Provided are methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders, including tumors and cancer. Also provided are methods of administering agonists or antagonists of IL-33 and IL-33 receptor.

Methods of modulating cytokine activity; related reagents

Methods of using pegylated interleukin-10 for treating cancer

Use of pegylated IL-10 to treat cancer

Method of treatment of lymphoma with pegylated IL-10

Method of treating solid cancers with pegylated IL-10

The present invention relates generally to uses of TSLP in the treatment of cancer.

Uses of mammalian cytokines and agonists; related reagents

Growing community of inventors

Palo Alto, CA, United States of America

Martin Oft