Yale University

Regeneron Pharmaceuticals, Inc.

Institute for Research in Biomedicine (irb)

The State University of New York

Ludwig Institute for Cancer Research Limited

Institute for Research in Biomedicine

Jorge E Galan

Andrew J Murphy

George D Yancopoulos

Sean Stevens

Richard A Flavell

Markus G Manz

Elizabeth Eynon

Anthony Rongvaux

Tim Willinger

Jeongmin Song

Lloyd J Old

Gerd J Ritter

Sacha Gnjatic

Heather Carleton

Hiroyoshi Nishikawa

Wolf-Dietrich Hardt

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mII2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/II2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g.,oris described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Genetically modified mice and engraftment

The invention provides compositions and methods for using PltA, PltB, CdtB, or a mutant thereof, in inducing or enhancing an immune response.

Compositions and methods for usingtoxin to induce or enhance an immune response

The invention provides compositions and methods for preventing, treating and diagnosing infection byserovar() and/or, i.e., typhoid fever.

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A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mll2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/ll2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g.,oris described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

The present invention provides compositions and methods for the secretion and the translocation of a compound of interest by a bacterial minicell. In certain embodiments, the invention provides a bacterial minicell comprising at least one component of the type III secretion system (T3SS), which provides a safe and efficient system for secretion and translocation. In one embodiment, the invention allows for the delivery of an antigen to a cell or subject in order to induce an immune response.

Non-replicating bacterial nanoparticle delivery system and methods of use

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g.,oris described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

The invention relates to the use of the type III secretion system of bacteria to stimulate immune responses against tumor antigen(s) for treating antigen-loss variant tumors. Methods are provided for stimulating and/or increasing an immune response against tumor antigens. The invention also relates to the preparation of antigen presenting cells from peripheral blood mononuclear cells using bacteria having a type III secretion system.

Methods for stimulating an immune response using bacterial antigen delivery system

Provided is a signal peptide comprising an amino acid sequence at least 90% homologous to the amino acid sequence as shown in SEQ ID NO:1. Further provided is a fusion protein comprising the signal peptide fused to a heterologous protein. Also provided are nucleic acid molecules encoding the signal peptide and encoding the fusion protein, as well as vectors and recombinant host cells comprising the nucleic acid molecules. The recombinant host cell can be a recombinant bacterium having a functional type III secretion system and having loss-of-function mutations in genes that encode secreted substrate proteins of the type III secretion system. The recombinant host cell can be used in a method of producing the heterologous protein.

System for efficient secretion of recombinant proteins

Provided is a method of stimulating a class I-restricted immune response to a protein of interest or antigenic portion thereof in a host, as well as a protein delivery vehicle for use in the method. A nucleic acid molecule encoding the protein of interest or antigenic portion thereof is introduced into an avirulent Salmonella spp., such that the resulting Salmonella encodes a chimeric protein comprising the protein of interest or antigenic portion thereof and an injectable protein which is a target of a type III secretion system or an injectable portion thereof. This resulting Salmonella can be introduced into a host, in which the Salmonella will inject the chimeric protein into the cytosol of the cells of the host. The injection of the chimeric protein results in the stimulation of a class I-restricted immune response to the protein of interest or antigenic portion thereof in the host.

Growing community of inventors

Strongs Neck, NY, United States of America

Jorge E Galan