Abstract: The disclosure features antagonistic TNFR superfamily polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the downstream signaling of TNFR superfamily members. The antibodies and antigen-binding fragments thereof can be used to treat a wide variety of cancers, infectious diseases, autoimmune disorders, obesity, type 2 diabetes, neurological disorders, and osteoporosis.

Abstract: The present invention relates to antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or expand T effector cell populations or function. For example, antibodies of the invention include antagonistic TNFR2 antibodies and antigen-binding fragments thereof, and can be used to suppress the T-reg-mediated deactivation of tumor reactive T-lymphocytes, as well as to treat a wide variety of cancers and infectious diseases.

Abstract: The invention features methods of producing compositions enriched in Tregs and methods for treating immunological disorders using these compositions. The invention also features methods for producing compositions enriched in lymphocytes and depleted of Tregs and the use of these compositions in the treatment of proliferative disorders.

Abstract: Described are antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or myeloid-derived suppressor cells (MDSCs), to expand T effector cell populations or function, and to reduce the proliferation of, or directly kill, tumor cells, such as tumor cells that express TNFR2 antigen. The polypeptides, such as antibodies and antigen-binding fragments thereof, are TNFR2 antagonists, such as dominant TNFR2 antagonists. The polypeptides can be used to suppress the T-reg- or MDSC-mediated deactivation of tumor reactive T lymphocytes, expand populations of tumor-reactive cytotoxic T cells, and/or to directly kill TNFR2+ tumor cells. The antagonistic TNFR2 polypeptides described herein can be used to treat a wide variety of cancers and infectious diseases.

Abstract: Described are antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or myeloid-derived suppressor cells (MDSCs), to expand T effector cell populations or function, and to reduce the proliferation of, or directly kill, tumor cells, such as tumor cells that express TNFR2 antigen. The polypeptides, such as antibodies and antigen-binding fragments thereof, are TNFR2 antagonists, such as dominant TNFR2 antagonists. The polypeptides can be used to suppress the T-reg- or MDSC-mediated deactivation of tumor reactive T lymphocytes, expand populations of tumor-reactive cytotoxic T cells, and/or to directly kill TNFR2+ tumor cells. The antagonistic TNFR2 polypeptides described herein can be used to treat a wide variety of cancers and infectious diseases.

Abstract: Described are agonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to stimulate the proliferation of regulatory T cells (Treg cells) and/or myeloid-derived suppressor cells (MDSCs), as well as to inhibit the function of, reduce the proliferation of, and/or directly kill, T effector cells, such as CD8+ T effector cells. The polypeptides, such as antibodies and antigen-binding fragments thereof, of the disclosure can be used, for example, to suppress autoimmunity and inflammation, as well as to promote the protection, healing, preservation, and/or regeneration of a wide variety of tissues and organs, such as tissues and organs containing TNFR2+ cells.

Abstract: Described are compositions and methods for determining the propensity of a subject with diabetes (e.g., type 1 diabetes) to benefit from treatment with Bacillus Calmette-Guerin (BCG). Using the compositions and methods of the disclosure, a subject with diabetes (e.g., type 1 diabetes) may be identified as likely to respond to BCG therapy on the basis, for example, of a determination that the subject was young (e.g., less than 40 years of age) at the time of onset of the diabetes. Additionally, or alternatively, the subject may be identified as likely to respond to BCG therapy based on a determination that the subject exhibits a reduced rate of glucose uptake, an elevated rate of oxidative phosphorylation, and/or a reduced rate of aerobic glycolysis, for example, as compared to a healthy subject (e.g., a subject without diabetes). The compositions and methods of the disclosure can additionally be used to administer BCG to subjects identified as likely to respond to treatment with a composition comprising BCG.

Abstract: The invention provides methods of treating disease, such as hypercholesterolemia (e.g., by modulating serum lipids, such as cholesterol, low-density lipoproteins, high-density lipoproteins, and triglycerides) and hyperglycemia by administering Bacillus Calmette-Guerin (BCG). Methods of the invention also encompass the use of genomic, proteomic, and metabolomic analyses for determining the likelihood that a patient has disease or will respond to treatment (e.g., with BCG therapy), as well as for determining whether a patient previously administered BCG would benefit from BCG redosing.

Abstract: The invention provides agonistic TNFR2 antibodies and antigen-binding fragments thereof and encompasses the use of these antibodies as therapeutics to promote the proliferation of regulatory T cells (T-reg) for the treatment of immunological diseases. Antibodies of the invention can be used to potentiate the T-reg-mediated deactivation of self- and allergen-reactive T- and B-lymphocytes, and can thus be used to treat a wide variety of indications, including autoimmune diseases, allergic reactions, asthma, graft-versus-host disease, and allograft rejection, among others.

Abstract: The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.

Abstract: The invention provides methods of treating disease, such as hypercholesterolemia (e.g., by modulating serum lipids, such as cholesterol, low-density lipoproteins, high-density lipoproteins, and triglycerides) and hyperglycemia by administering Bacillus Calmette-Guerin (BCG). Methods of the invention also encompass the use of genomic, proteomic, and metabolomic analyses for determining the likelihood that a patient has disease or will respond to treatment (e.g., with BCG therapy), as well as for determining whether a patient previously administered BCG would benefit from BCG redosing.

Abstract: Described are agonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to stimulate the proliferation of regulatory T cells (Treg cells) and/or myeloid-derived suppressor cells (MDSCs), as well as to inhibit the function of, reduce the proliferation of, and/or directly kill, T effector cells, such as CD8+ T effector cells. The polypeptides, such as antibodies and antigen-binding fragments thereof, of the disclosure can be used, for example, to suppress autoimmunity and inflammation, as well as to promote the protection, healing, preservation, and/or regeneration of a wide variety of tissues and organs, such as tissues and organs containing TNFR2+ cells.

Abstract: Described are antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or myeloid-derived suppressor cells (MDSCs), to expand T effector cell populations or function, and to reduce the proliferation of, or directly kill, tumor cells, such as tumor cells that express TNFR2 antigen. The polypeptides, such as antibodies and antigen-binding fragments thereof, are TNFR2 antagonists, such as dominant TNFR2 antagonists. The polypeptides can be used to suppress the T-reg- or MDSC-mediated deactivation of tumor reactive T lymphocytes, expand populations of tumor-reactive cytotoxic T cells, and/or to directly kill TNFR2+ tumor cells. The antagonistic TNFR2 polypeptides described herein can be used to treat a wide variety of cancers and infectious diseases.

Abstract: Antagonistic TNFR superfamily polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs). For example, antibodies of the invention include antagonistic TNER2 antibodies and antigen-binding fragments thereof, and can be used to suppress the T-reg-mediated deactivation of tumor reactive T-lymphocytes, as well as to treat a wide variety of cancers and infectious diseases.

Abstract: The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.

Abstract: Antagonistic TNFR superfamily polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs). For example, antibodies of the invention include antagonistic TNFR2 antibodies and antigen-binding fragments thereof, and can be used to suppress the T-reg-mediated deactivation of tumor reactive T-lymphocytes, as well as to treat a wide variety of cancers and infectious diseases.

Abstract: The invention features methods of producing compositions enriched in Tregs and methods for treating immunological disorders using these compositions. The invention also features methods for producing compositions enriched in lymphocytes and depleted of Tregs and the use of these compositions in the treatment of proliferative disorders.

Abstract: The invention features methods of producing compositions enriched in Tregs and methods for treating immunological disorders using these compositions. The invention also features methods for producing compositions enriched in lymphocytes and depleted of Tregs and the use of these compositions in the treatment of proliferative disorders.

Abstract: Described are antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or myeloid-derived suppressor cells (MDSCs), to expand T effector cell populations or function, and to reduce the proliferation of, or directly kill, tumor cells, such as tumor cells that express TNFR2 antigen. The polypeptides, such as antibodies and antigen-binding fragments thereof, are TNFR2 antagonists, such as dominant TNFR2 antagonists. The polypeptides can be used to suppress the T-reg- or MDSC-mediated deactivation of tumor reactive T lymphocytes, expand populations of tumor-reactive cytotoxic T cells, and/or to directly kill TNFR2+ tumor cells. The antagonistic TNFR2 polypeptides described herein can be used to treat a wide variety of cancers and infectious diseases.

Abstract: The present invention relates to antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or expand T effector cell populations or function. For example, antibodies of the invention include antagonistic TNFR2 antibodies and antigen-binding fragments thereof, and can be used to suppress the T-reg-mediated deactivation of tumor reactive T-lymphocytes, as well as to treat a wide variety of cancers and infectious diseases.