Fred Hutchinson Cancer Center

Amazon Technologies, Inc.

Adaptive Biotechnologies Corporation

University of Illinois

University of Washington

Fred Hutchinson Cancer Research Center

Thomas M Schmitt

Philip D Greenberg

Aude Georgiana Chapuis

Shannon K Oda

Harlan Saul Robins

Anna M Sherwood

Nare Alan Hayrapetyan

Kai Steffen Gorman

Megan McAfee

Tijana Martinov

Ingunn M Stromnes

Rachel Perret

David Martin Koelle

David M Kranz

Andrew Thomas Troutman

Robert Allan Brigham, Ii

Nathaniel Gaertner

Sheena N Smith

Luis Alejandro Acosta

Daniel T Harris

Karan Kapoor

Karen Kapoor

Jitendra Singh Rajput

Hieu Nguyen

Paul T Nghiem

Natalie J Miller

Kelly Garneski Paulson

Candice Church

Kenneth William Exner

Anna Sherwood

The present disclosure provides T cell receptors (TCRs) and related binding proteins with high functional avidity against tumor associated antigen p37 from Wilms tumor protein 1 (WT1), T cells expressing such high affinity WT1 specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress WT1 and/or produce the p37 antigen, such as in cancer.

High avidity WT1 T cell receptors and uses thereof

The present disclosure relates to immunomodulatory fusion proteins containing an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a modulatory signal in a host cell, such as a T cell. The present disclosure also relates to uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease.

Immunomodulatory fusion proteins and uses thereof

Described herein are immunomodulatory fusion proteins containing an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a modulatory signal in a host cell, such as a T cell. Some immunomodulatory fusion proteins as described comprise a SIRPα extracellular component and hydrophobic and intracellular components comprising transmembrane and/or signaling domains of a CD28, respectively. Such fusion proteins are capable of delivering a positive or costimulatory signal in response to a binding event that in a natural setting would result in an inhibitory signal. Uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease, are also described.

The present disclosure provides binding proteins and TCRs with high affinity and specificity against Merkel cell polyomavirus T antigen epitopes or peptides, T cells expressing such high affinity Merkel cell polyomavirus T antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating Merkel cell carcinoma.

High affinity merkel cell polyomavirus T antigen-specific TCRS and uses thereof

The present disclosure provides compositions and methods for targeting a Ras antigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as a T cell receptor or a chimeric antigen receptor, that bind to a Ras antigen:HLA complex. Polynucleotides encoding such binding protein can introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers. Also provided are immunogenic polypeptides that can be useful to, for example, induce an immune response against a mutated Ras or to identify a binding protein that binds to a Ras antigen.

Binding proteins specific for RAS neoantigens and uses thereof

Methods are provided for identifying T cell receptors that specifically bind a particular antigenic target and can be used as therapeutics against disease.

Method of identifying human compatible T cell receptors specific for an antigenic target

The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human MAGE-A1 epitopes), T cells expressing such high affinity antigen-specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.

High affinity MAGE-A1-specific TCRs and uses thereof

The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human Wilms tumor protein 1 (WT 1) epitopes and mesothelin epitopes), T cells expressing such high affinity antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.

High affinity T cell receptors and uses thereof

The present disclosure provides methods for generating enhanced affinity T cell receptors by agonist selection of hematopoietic progenitor cells expressing an antigen specific TCR&#x3b1; cultured with stromal cells expressing Delta-like-1 or Delta-like-4, compositions prepared from such methods, and uses of thereof.

Enhanced affinity T cell receptors and methods for making the same

The present disclosure provides high affinity and enhanced affinity T cell receptors specific for human Wilms tumor protein 1 (WT-1) epitopes for use in treating diseases or disorders, such as cancer cells that overexpress WT-1.

T cell immunotherapy specific for WT-1

T cell receptors (TCRs) that have specificity for the WT1 antigen are provided. The TCRs include higher affinity TCRs that were engineered through the generation of mutational libraries of TCRs in a single-chain format, followed by selection for improved stability and affinity on the surface of yeast (i.e. directed evolution). In embodiments, the TCRs can be used in soluble form for targeted delivery in vivo, or as genes introduced into T cells in an adoptive T cell setting.

Engineered high-affinity human t cell receptors

Technologies are disclosed herein for automated software release lifecycle management. In particular, a software release management network service is disclosed that provides functionality for allowing a software developer to automate aspects of a software release pipeline. A software release pipeline can have multiple stages, each of which can have multiple actions. The actions can include internal actions that utilize network services internal to a service provider network. The actions can also include external actions that utilize network services that are external to a service provider network. The internal and external actions can perform various release-related functions, such as obtaining source code, building the source code, deploying built program code, and for performing tests. Stage gates and/or action gates can also be defined for conditional execution of the next stage or action in a software release pipeline, respectively. A gate bypass can also be specified to override stage or action gates.

Growing community of inventors

Seattle, WA, United States of America

Thomas M Schmitt