Abstract: A novel costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefor and expression vectors comprising this DNA. B7-DC protein, fragments, fusion polypeptides/proteins and other functional derivatives, and transformed cells expressing B7-DC are useful in vaccine compositions and methods. Compositions and methods are disclosed for inducing potent T cell mediated responses that can be harnessed for anti-tumor and anti-viral immunity.

Abstract: Combinations of anti-cancer antibodies and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

Abstract: We formulated multiple TLR agonists into GVAX (lethally irradiated tumor cell vaccines engineered to secrete GM-CSF). Specifically, GLA and R848, TLR4 and TLR7/8 agonists found to be safe in patients, were formulated with GVAX (TEGVAX—for TLR agonists enhanced GVAX), and this formulation was effective in producing anti-tumor responses in 3 different preclinical models, including palpable B16. These anti-tumor responses were correlated with increased CD4 and CD8 T-cells that can secrete IFN? circulating in the tumor microenvironment as well as significantly higher level of p15E specific CTL mediated cell killing in mice treated with TEGVAX in comparison to controls. When combined with anti-PD-1 antibody, TEGVAX was able to induce regression of established B16 tumors.

Abstract: The invention provides provides immunogenic compositions comprising neoplastic cells expressing a cytokine (GM-CSF) formulated with at least one TLR agonist and methods of using the composition to induce or enhance an immune response.

Abstract: An approach combining immune-based therapies with focused radiation, including stereotactic radiation, to treat cancers is disclosed. The use of focused radiation primes the immune system in a similar manner to vaccines to augment immune-based therapies and can counteract the suppressive effects of a tumor. The combination of focused radiation and immune-based therapies, including administration of at least one immunotherapeutic agent, improves survival compared to each therapy alone and can, in some cases, lead to a durable cure. Accordingly, focused radiation can be an adjuvant for immune-based therapies for treating cancers.

Abstract: Mammals with cancer are treated with an antibody which specifically binds to CD223 protein and inhibits negative T cell regulatory function of CD223. The mammal may be a human. The antibody may be a monoclonal antibody. The amount of the antibody administered may be sufficient to enhance an immune T cell response to the cancer.

Abstract: The present invention provides a combination therapy which relies on a small molecule immune stimulator—cyclic-di-nucleotide (CDN)—that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes) formulated with allogeneic human tumor cell lines engineered to secrete high amounts of GM-CSF. This combination therapy can provide an ideal synergy of multiple tumor associated antigens, DC recruitment and proliferation, coupled with a potent DC activation stimulus.

Abstract: We formulated multiple TLR agonists into GVAX (lethally irradiated tumor cell vaccines engineered to secrete GM-CSF). Specifically, GLA and R848, TLR4 and TLR7/8 agonists found to be safe in patients, were formulated with GVAX (TEGVAX—for TLR agonists enhanced GVAX), and this formulation was effective in producing anti-tumor responses in 3 different preclinical models, including palpable B16. These anti-tumor responses were correlated with increased CD4 and CD8 T-cells that can secrete IFN? circulating in the tumor microenvironment as well as significantly higher level of p15E specific CTL mediated cell killing in mice treated with TEGVAX in comparison to controls. When combined with anti-PD-1 antibody, TEGVAX was able to induce regression of established B16 tumors.

Abstract: The invention generally features compositions and methods for modulating an immune response. In particular embodiments, such compositions and methods modulate regulatory T cell suppressive activity.

Abstract: We demonstrate herein that neuritin controls the homeostasis of regulatory T cells in an antigen dependent manner. Based on this discovery, we describe herein the application of neuritin as a therapeutic agent to manipulate antigen specific regulatory T cells in various disease settings is described. Thus manipulation of Treg cells and DCs through neuritin can be used to enhance immunotherapy of autoimmune diseases, cancer and infectious diseases, as well as enhance lymphocyte engraftment in settings of donor lymphocyte infusion, bone marrow transplant, as well as other types of transplants, and adoptive transfer.

Abstract: An approach combining immune-based therapies with focused radiation, including stereotactic radiation, to treat cancers is disclosed. The use of focused radiation primes the immune system in a similar manner to vaccines to augment immune-based therapies and can counteract the suppressive effects of a tumor. The combination of focused radiation and immune-based therapies, including administration of at least one immunotherapeutic agent, improves survival compared to each therapy alone and can, in some cases, lead to a durable cure. Accordingly, focused radiation can be an adjuvant for immune-based therapies for treating cancers.

Abstract: Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

Abstract: A novel costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefor and expression vectors comprising this DNA. B7-DC protein, fragments, fusion polypeptides/proteins and other functional derivatives, and transformed cells expressing B7-DC are useful in vaccine compositions and methods. Compositions and methods are disclosed for inducing potent T cell mediated responses that can be harnessed for anti-tumor and anti-viral immunity.

Abstract: Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

Abstract: The invention provides provides immunogenic compositions comprising neoplastic cells expressing a cytokine (GM-CSF) formulated with at least one TLR agonist and methods of using the composition to induce or enhance an immune response.

Abstract: A novel costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefor and expression vectors comprising this DNA. B7-DC protein, fragments, fusion polypeptides/proteins and other functional derivatives, and transformed cells expressing B7-DC are useful in vaccine compositions and methods. Compositions and methods are disclosed for inducing potent T cell mediated responses that can be harnessed for anti-tumor and anti-viral immunity.

Abstract: A novel costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefore and expression vectors comprising this DNA. B7-DC protein, fragments, fusion polypeptides/proteins and other functional derivatives, and transformed cells expressing B7-DC are useful in vaccine compositions and methods. Compositions and methods are disclosed for inducing potent T cell mediated responses that can be harnessed for anti-tumor and anti-viral immunity.

Abstract: The invention provides compositions and methods for useful for the diagnosis of inflammatory bowel disease, ETBF-induced colitis, colonic hyperplasia and/or colon carcinogenesis in a subject in biological samples (e.g., stool, urine, blood, serum, tissue). The invention further provides compositions and methods for the treatment or prevention of colitis, colon cancer, or inflammatory bowel disease (e.g., Crohn's disease).

Abstract: A novel costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefor and expression vectors comprising this DNA. B7-DC protein, fragments, fusion polypeptides/proteins and other functional derivatives, and transformed cells expressing B7-DC are useful in vaccine compositions and methods. Compositions and methods are disclosed for inducing potent T cell mediated responses that can be harnessed for anti-tumor and anti-viral immunity.

Abstract: A novel costimulatory protein molecule, B7-DC, which is a member of the B7 family, is described as is DNA coding therefor and expression vectors comprising this DNA. B7-DC protein, fragments, fusion polypeptides/proteins and other functional derivatives, and transformed cells expressing B7-DC are useful in vaccine compositions and methods. Compositions and methods are disclosed for inducing potent T cell mediated responses that can be harnessed for anti-tumor and anti-viral immunity.