Abstract: The invention provides a tumor cell genetically modified to express a nucleic acid encoding a secreted form of a heat shock protein (hsp) gp96 polypeptide. The invention also provides a method of stimulating an immune response to a tumor by administering a tumor cell genetically modified to express a nucleic acid encoding a secreted form of a gp96 polypeptide.

Abstract: The present invention relates to methods for purifying immunogenic, prophylactically and therapeutically effective complexes of modified heat shock proteins noncovalently associated with antigenic peptides of cancer or infected cells. The claimed methods comprise the constructing of a nucleotide sequence encoding a secretable modified heat shock protein, expressing the sequence in an appropriate host cell, recovering the immunogenic complexes from the cell culture and the cells, and purifying the immunogenic complexes by affinity chromatography. Large amounts of such immunogenic complexes can be obtained by large-scale culturing of host cells containing the genetic sequence. The complexes can be used as a vaccine to elicit specific immune responses against cancer or infected cells, and to treat or prevent cancer or infectious diseases.

Abstract: Compositions are provided comprising heat shock protein, immunoglobulins and retroviral antigens to induce systemic and mucosal immunity to infection from retroviruses such as Human Immunodeficiency Virus (HIV). Methods of treatment provided comprise administration of the compositions, which boost the immune systems response to the retroviral antigens or immunogens.

Abstract: Compositions comprising TL1A-Ig fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin).

Abstract: Compositions comprising TL1A-Ig fusion proteins and methods of their use, e.g., for the treatment of diseases and disorders associated with antigen-specific immune responses, are described. Also described are combination therapies that include the administration of a TNFRSF25 agonist and an interleukin (e.g., IL-2) and/or an mTOR inhibitor (e.g., rapamycin).

Abstract: The present invention relates to methods for purifying immunogenic, prophylactically and therapeutically effective complexes of modified heat shock proteins noncovalently associated with antigenic peptides of cancer or infected cells. The claimed methods comprise the constructing of a nucleotide sequence encoding a secretable modified heat shock protein, expressing the sequence in an appropriate host cell, recovering the immunogenic complexes from the cell culture and the cells, and purifying the immunogenic complexes by affinity chromatography. Large amounts of such immunogenic complexes can be obtained by large-scale culturing of host cells containing the genetic sequence. The complexes can be used as a vaccine to elicit specific immune responses against cancer or infected cells, and to treat or prevent cancer or infectious diseases.

Abstract: Compositions of genetically engineered, secreted gp96 (gp69-Ig) induced strong mucosal and systemic immune responses and CD8 expansion that was independent of CD4 help. Immunization of patients with gp96-Ig immunization is especially attractive for induction of mucosal and systemic immunity to SIV/HIV and other diseases.

Abstract: Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a specific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.

Abstract: Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a specific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.

Abstract: The invention provides a method of modulating a T cell immune response by modulating DR3 function in the T cell, wherein the T cell response causes a symptom of inflammatory lung disease. The invention also provides a method of treating a reactive airway disease in an animal subject by administering to the subject an agent which modulates at least one functional activity of CD30. The invention additionally provides a method for treating an inflammatory lung disease by administering an agent that decreases the activity of DR3 or CD30, whereby IL-13 expression is decreased.

Abstract: Compositions and methods utilizing immunomodulating agents can either stimulate or indirectly augment the immune system or have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used to treat disease caused by asthma and chronic inflammation such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein are capable of inhibiting CD8 T cell-mediated cellular immune responses and can for example, mitigate organ or tissue rejection following a tissue transplantation.

Abstract: Compositions specific for TNF-receptor superfamily member 25 (TNFRSF25, DR3) modulate the immune response by regulating T regulatory cells.

Abstract: TNFR25 compositions enhance the immune response against antigens. Administration of TNFR25 agonists was found to enhance tumor rejection, responses against viral diseases and other infectious organisms.

Abstract: A cell-based vaccine prolongs the survival of cancer patients. The vaccine includes a dose of irradiated cultured lung adenocarcinoma cells (AD100) transfected with HLA A1 and gp96-Ig (human gp96 wherein the endoplasmic reticulum retention signal, KDEL, is replaced with the Fc-portion of human IgG1 and was injected intradermally into patients suffering from advanced, relapsed, or metastatic NSCLC. Administration of the vaccine increased the mean survival time of the patients compared to that of similar patients treated with placebo. Moreover, the immune response of patients to the vaccine (antigen-induced interferon gamma production by T cells) correlated with the survival times.

Abstract: Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a specific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.

Abstract: It is an object of the invention to provide novel compositions and methods utilizing immunomodulating agents that can either stimulate or indirectly augment the immune system or in other cases have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used, among other things, to treat disease caused by asthma and chronic inflammation such as for example inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein are capable of inhibiting CD8 T cell-mediated cellular immune responses and can for example, mitigate organ or tissue rejection following a tissue transplantation. TNFR25 agonists disclosed herein represent biological response modifiers that alter the interaction between the body's cellular immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the cancer when given with tumor vaccines.

Abstract: Compositions of genetically engineered, secreted gp96 (gp69-Ig) induced strong mucosal and systemic immune responses and CD8 expansion that was independent of CD4 help. Immunization of patients with gp96-Ig immunization is especially attractive for induction of mucosal and systemic immunity to SIV/HIV and other diseases.

Abstract: Compositions comprising TNF receptor super-family member 25 (TNFR25) agents, attenuate Treg activity and, by comparison with other TNFR members, only weakly costimulates T effector cell (Teff) activity. Alternatively spliced TNFR25 modulates the functional effects of TNFR25 signaling These agents have a wide therapeutic applicability in the treatment of diseases by modulating immune responses. In addition these agents can be used in conjunction with vaccines to enhance the immune response.

Abstract: The invention provides a tumor cell genetically modified to express a nucleic acid encoding a secreted form of a heat shock protein (hsp) gp96 polypeptide. The invention also provides a method of stimulating an immune response to a tumor by administering a tumor cell genetically modified to express a nucleic acid encoding a secreted form of a gp96 polypeptide.

Abstract: The invention provides a tumor cell genetically modified to express a nucleic acid encoding CD80 (B7.1) and a nucleic acid encoding an HLA antigen. The invention also provides a method of stimulating an immune response to a tumor by administering an allogeneic tumor cell such as a lung cancer cell genetically modified to express a nucleic acid encoding CD80 (B7.1) and a nucleic acid encoding an HLA antigen. The invention additionally provides a method of inhibiting a tumor by administering an allogeneic tumor cell such as a lung cancer cell genetically modified to express a nucleic acid encoding CD80 (B7.1) and a nucleic acid encoding an HLA antigen.