Abstract: The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK?) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.

Abstract: The present disclosure relates to infection-competent, but nonreplicative inactivated modified vaccinia Ankara (MVA) and its use as immunotherapy, alone, or in combination with immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to inducing an immune response in a subject diagnosed with a solid malignant tumor.

Abstract: Systems and methods for determining the likely responsiveness of a human cancer subject to a checkpoint blockade immunotherapy regimen are provided. Sequencing reads are obtained from samples from the subject representative of the cancer. A human leukocyte antigen type and a plurality of clones is determined from the sequencing reads. For each clone, an initial frequency X? in the one or more samples is determined and a corresponding clone fitness score of the clone is computed, thereby computing clone fitness scores. Each such fitness score is computed by identifying neoantigens in the respective clone, computing a recognition potential for each neoantigen, and determining the corresponding clone fitness score of the respective clone as an aggregate of these recognition potentials. A total fitness, quantifying the likely responsiveness of the subject to the regimen, is computed by summing the clone fitness scores across the plurality of clones.

Abstract: The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVA?E3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.

Abstract: The present disclosure relates to infection-competent, but nonreplicative inactivated modified vaccinia Ankara (MVA) and its use as immunotherapy, alone, or in combination with immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to inducing an immune response in a subject diagnosed with a solid malignant tumor.

Abstract: The present disclosure provides antibodies that specifically bind to human GITR, as well as compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and deactivate, reduce, or inhibit GITR activity. The present disclosure also provides methods for treating autoimmune or inflammatory diseases disorders, by administering an antibody that specifically binds to human GITR and deactivates, reduces, or inhibits GITR activity.

Abstract: The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or reduce, deactivate, or inhibit OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., reduces, deactivates, or inhibits OX40 activity.

Abstract: The immune response to melanoma cells and tumors can be induced or significantly increased by administering to a subject a pharmaceutical composition comprising alphavirus particles, especially Venezuelan equine encephalitis virus replicon particles, which express the melanoma antigen dopachrome tautomerase (DCT, TRP2) in cells of the subject, with the result of tumor regression and/or inhibition of metastasis of a melanoma subject, or a decreased risk of the occurrence or recurrence of melanoma and/or decreased severity of melanoma in a subject not suffering from melanoma at the time of administration. The pharmaceutical composition described herein can be used in conjunction with other therapeutic agents, it can be administered on more than one occasion and it can be combined with administrations of other compositions such as protein or other immunogenic compositions, and/or adjuvants, with beneficial effects to the human or animal subject to which it has been administered.

Abstract: The present disclosure provides multispecific (e.g., bispecific) antibodies that specifically bind to human GITR and/or human OX40 as well as compositions comprising such antibodies. In a specific aspect, the multispecific antibodies specifically bind to human GITR and OX40 and modulate GITR and/or OX40 activity, e.g., enhance, activate, or induce GITR and/or OX40 activity, or reduce, deactivate, or inhibit GITR and/or OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., enhances, activates, or induces GITR and/or OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., reduces, deactivates, or inhibits GITR and/or OX40 activity.

Abstract: The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or diminish, deactivate, or suppress OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., diminishes, deactivates, or suppresses OX40 activity.

Abstract: The present invention provides various compositions and methods useful for the treatment of cancer, such as cancers that are resistant to immune checkpoint blockade and/or are resistant to treatment with PD-1, PD-L1 or CTLA-4 inhibitors. In some embodiments the present invention provides compositions comprising one or more CD40 agonists (e.g. CD40 agonist antibodies), TLR agonists, and/or IL10 receptor inhibitors or IL10 inhibitors, and/or various combinations thereof, optionally together with one or more immune checkpoint inhibitors, and the use of such compositions in treatment of tumors.

Abstract: The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Abstract: The present invention provides various compositions and methods useful for the treatment of cancer, including, but not limited to, cancers that are resistant to immune checkpoint blockade and/or are resistant to treatment with PD-1, PD-L1 or CTLA-4 inhibitors. In some embodiments the present invention provides compositions comprising “bi-specific activators”—which are nanoparticles having both a CD40 agonist antibody and an antibody specific for a tumor-associated antigen on their surface. In some embodiments such nanoparticles comprise one or more vaccine adjuvants, for example inside the nanoparticles. The present invention also relates to the use of such compositions in the treatment of tumors.

Abstract: The present disclosure relates to modified vaccinia Ankara (MVA) virus or MVAAE3L delivered intratumorally or systemically as an anticancer immunotherapeutic agent, alone, or in combination with one or more immune checkpoint blocking agents for the treatment of malignant solid tumors. Particular embodiments relate to mobilizing the host's immune system to mount an immune response against the tumor.

Abstract: Provided are antibodies that specifically bind to CTLA-4 and/or PD-1 and antagonize CTLA-4 and/or PD-1 function. Also provided are pharmaceutical compositions and kits comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies either alone or in combination.

Abstract: The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK?) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.

Abstract: The presently disclosed subject matter provides methods and compositions for treating cancer (e.g., melanoma). It relates to chimeric antigen receptors (CARs) that specifically target MDA (e.g., Trp1), and immunoresponsive cells comprising such CARs. The presently disclosed MDA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and/or human GITR receptor (GITR), including multispecific antibodies that bind, e.g., to OX40 and GITR, and compositions comprising such antibodies. The antibodies disclosed herein modulate OX40 and/or GITR activity e.g., enhance, activate, induce, reduce, deactivate, or inhibit OX40 and/or GITR activity. The present disclosure also provides methods for treating disorders, such as cancer, autoimmune diseases or disorders, or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and/or human GITR and modulates OX40 and/or GITR activity.

Abstract: The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or reduce, deactivate, or inhibit OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., reduces, deactivates, or inhibits OX40 activity.

Abstract: The instant disclosure provides antibodies that specifically bind to human CTLA-4 and antagonize CTLA-4 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.