Dana-Farber-Cancer Institute Inc.

The General Hospital Corporation

The General Hospital Corporation D/b/a Massachusetts General Hospital

Harvey I Cantor

Hye-Jung Kim

Gary J Nabel

Roberto M Patarca

Glenn Dranoff

Nir Hacohen

Kai W Wucherpfennig

Donald Raymond Shaffer

Diana Alvarez Arias

Penghui Zhou

Jianmei Wu Leavenworth

Gordon James Freeman

Joel L Schwartz

Xiao-Feng Yang

Georg F Weber

Jessica M Sido

Linrong Lu

Nami McCarty

Provided by the disclosure are compositions and methods for modulating differentiation of regulatory T cells. In some embodiments, methods include selectively decreasing IL-23R activity and/or IL-23R expression without significantly decreasing IL-12Rβ activity and/or IL-12Rβ expression.

IL-23R antagonists to reprogram intratumoral T regulatory cells into effector cells

The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.

Methods and compositions for reducing immunosuppression by tumor cells

Provided by the disclosure are compositions and methods for modulating differentiation of regulatory T cells. In some embodiments, methods include selectively decreasing IL-23R activity and/or IL-23R expression without significantly decreasing IL-12RP activity and/or IL-12RP expression.

Nanoparticles to treat autoimmune diseases and HIV infection are provided. The nanoparticles comprise a biocompatible polymer and a complex, wherein the complex is a major histocompatibility complex (MHC) class I antigen E (HLA-E) linked to a peptide, and wherein the HLA-E-peptide complex is linked to the surface of the nanoparticle. The present invention also relates to methods for treating autoimmune diseases and HIV infection.

Targeted expansion of Qa-1-peptide-specific regulatory CD8 T cells to ameliorate arthritis

Methods for diagnosing and prognosing autoimmune diseases and T cell lymphomas are provided, for example by measuring levels of intracellular osteopontin (OPN-i). Also provided are screening methods for identifying activators and inhibitors of the transcription factor Bcl6, which is involved in T cell activation/differentiation. Other aspects of the disclosure provide methods for enhancing adoptive T cell transfer.

Intracellular osteopontin regulates the lineage commitment of lymphoid subsets

Methods and compositions for reducing immunosupression by tumor cells

A method to treat an autoimmune disease is provided. The method involves administration of interleukin-15 receptor (IL-15R) agonists in an amount effective to ameliorate a symptom of the autoimmune disease. The invention also involves a method to treat an autoimmune disease by ex-vivo expansion of CD44+CD122+Kir+ CD8+ Treg cells and administration of the CD44+CD122+Kir+ CD8+ Treg cells. Compositions comprising CD44+CD122+Kir+ CD8+ Treg cells are also provided. Methods for stimulating an immune response to an antigen are also provided.

Discovery of regulatory T cells programmed to suppress an immune response

The invention relates to compositions and methods used to assess and alter the expression and activity of MINK in cells of the immune system, particularly thymocytes and T lymphocytes. The methods and compositions are used in a variety of clinical applications including vaccination, treatment of cancer, infectious disease, allergy, and transplantation. Screening methods are provided to identify inhibitors of MINK and susceptibility to effects of under- or over-expression of MINK.

Regulation of mink in thymocytes and T lymphocytes

The present invention relates to BCL-x&#x3b3;, a novel isoform of the BCL-x family of proteins which is predominantly expressed in T-lymphocytes and is associated with resistance to apoptosis. Both compositions of matter and methods are described which are useful in the treatment or prevention of immune system disorders.

BCL-x&#x3b3;, a novel BCL-x isoform, and uses related thereto

The present invention relates to BCL-x&ggr;, a novel isoform of the BCL-x family of proteins which is predominantly expressed in T-lymphocytes and is associated with resistance to apoptosis. Both compositions of matter and methods are described which are useful in the treatment or prevention of immune system disorders.

BCL-XY, a novel BCL-X isoform, and uses related thereto

The present invention relates to genes and their encoded proteins which induce immunological effector cell activation and chemattraction. The proteins of the invention attract subsets of immunological effector cells and stimulate them to express their specialized effector cell functions. Such proteins, termed Ap-1 proteins, are expressed by lymphoid cells, and bind to effector cells such as macrophages and mast cells. In particular, the Ap

Nucleic Acids Encoding proteins which induce immunological effector cell

The present invention is directed to genes, termed Rpt-1 (regulatory protein T lymphocyte-1), which are expressed at higher levels by resting CD4.sup.+ helper/inducer T cells relative to activated CD4.sup.+ cells. The invention also relates to the proteins encoded by such genes, termed rpt-1 proteins, which regulate gene expression directed by the promoter region of the interleukin-2 receptor (IL-2r) alpha chain gene or by the promoter region of the long terminal repeat of human lymphotropic retroviruses such as the human immunodeficiency virus type 1 (HIV-1), human T cell leukemia virus (HTLV-I, and HTLV-II. In particular, rpt-1 proteins down-regulate gene expression controlled by the promoter of the IL-2r alpha chain gene or by the promoter of the long terminal repeat of HIV-1. The proteins and nucleic acids of the invention have value in diagnosis and therapy of immune disorders such as AIDS. In a specific example of the present invention, an Rpt-1 gene and its encoded intracellular protein of approximately 41,000 daltons molecular weight are described. The rpt-1 protein is shown to be selectively expressed by activated CD4.sup.+ T cells, and to down-regulate gene expression of the IL-2r and the HIV-1.

Proteins which regulate gene expression of the interleukin-2 receptor

The present invention relates to genes and their encoded proteins which induce immunological effector cell activation and chemattraction. The proteins of the invention attract subsets of immunological effector cells and stimulate them to express their specialized effector cell functions. Such proteins, termed Ap-1 proteins, are expressed by lymphoid cells, and bind to effector cells such as macrophages and mast cells. In particular, the Ap-1 proteins induce macrophage phagocytosis, expression of class II major histocompatibility molecules, cytotoxicity, and migration, and induce hematopoietic progenitor cell differentiation. The Ap-1 molecules can be of value in the therapy or diagnosis of inflammatory or immune disorders, or neoplasia.

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Wellesley, MA, United States of America

Harvey I Cantor