Abstract: The present invention provides various CD40 binding molecules (including, but not limited to, antibodies), compositions comprising such CD40 binding molecules, and methods of using such CD40 binding molecules and compositions, for example for CD40-mediated activation of cells, such as antigen presenting cells.

Abstract: Provided are methods of assigning a LAG+, LAG?, or PRO immunotype to a cancer patient based on the frequencies of LAG-3+CD8+T-cells, Ki67+CD8+T-cells, Tim-3+CD8+T-cells, and ICOS+CD8+T-cells in a peripheral blood sample from the patient, and selecting an anti-cancer therapy, for example, an immune checkpoint blockade (ICB) therapy, based on the patient's immunotype.

Abstract: The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target GD3 and cells comprising such GD3-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the GD3-targeted antigen-recognizing receptors for treatment.

Abstract: In some aspects, the present invention provides heteroclitic CALRMUT peptides designed and selected to elicit an immune response to CALRMUT in subjects with JAK2 mutant-negative myeloproliferative neoplasms, nucleic acid molecules encoding such peptides, compositions comprising such peptides or nucleic acid molecules, and various associated compositions and methods.

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 invention relates to methods and compositions for identifying subjects treated with or considered for treatment with checkpoint blockade therapeutic agents that are at higher or lower risk for developing checkpoint therapy associated colitis, by analyzing the intestinal microbiome of those subjects. It is based, at least in part, on the discovery that the abundance of certain intestinal microbiota of the phyla Bacteroidetes, including the bacteria in the families Bacteroidaceae, Rikenellaceae, and Barnesisllaceae, and/or an increase or decrease in microbial genetic pathways involved in polyamine transport and/or B vitamin biosynthesis (e.g., (riboflavin (B2), pantothenate (B5) and thiamine (B1)) are associated with the likelihood of developing checkpoint therapy associated colitis.

Abstract: Described herein are nanoparticle conjugates that demonstrate enhanced penetration of tumor tissue (e.g., brain tumor tissue) and diffusion within the tumor interstitium, e.g., for treatment of cancer. Further described are methods of targeting tumor-associated macrophages, microglia, and/or other cells in a tumor microenvironment using such nanoparticle conjugates. Moreover, diagnostic, therapeutic, and theranostic (diagnostic and therapeutic) platforms featuring such nanoparticle conjugates are described for treating targets in both the tumor and surrounding microenvironment, thereby enhancing efficacy of cancer treatment. Use of the nanoparticle conjugates described herein with other conventional therapies, including chemotherapy, radiotherapy, immunotherapy, and the like, is also envisaged.

Abstract: The present invention relates to methods and compositions for identifying subjects treated with or considered for treatment with checkpoint blockade therapeutic agents that are at higher or lower risk for developing checkpoint therapy associated colitis, by analyzing the intestinal microbiome of those subjects. It is based, at least in part, on the discovery that the abundance of certain intestinal microbiota of the phyla Bacteroidetes, including the bacteria in the families Bacteroidaceae, Rikenellaceae, and Barnesisllaceae, and/or an increase or decrease in microbial genetic pathways involved in polyamine transport and/or B vitamin biosynthesis (e.g., (riboflavin (B2), pantothenate (B5) and thiamine (B1)) are associated with the likelihood of developing checkpoint therapy associated colitis.

Abstract: The technology of the present disclosure relates to the use of Heat-inactivated modified vaccinia Ankara (MVA) vims (Heat-iMVA) or Heat-inactivated vaccinia vims as a vaccine immune adjuvant. In particular, the present technology relates to the use of Heat-iMVA as a vaccine adjuvant for tumor antigens in cancer vaccines alone or in combination with immune checkpoint blockade (ICB) antibodies for use as a cancer immunotherapeutic.

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 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 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 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: Described herein are chimeric Newcastle disease viruses comprising a packaged genome comprising a transgene encoding interleukin-12. The chimeric Newcastle disease viruses and compositions thereof are useful in combination with an antagonist of programmed cell death protein 1 (“PD-1”) or a ligand thereof in the treatment of cancer. In particular, described herein are methods for treating cancer comprising administering the chimeric Newcastle disease viruses in combination with an antagonist of PD-1 or a ligand thereof, wherein the chimeric Newcastle disease virus comprises a packaged genome comprising a transgene encoding interleukin-12.

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 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: Described herein are chimeric Newcastle disease viruses engineered to express an agonist of a co-stimulatory signal of an immune cell and compositions comprising such viruses. Also described herein are chimeric Newcastle disease viruses engineered to express an antagonist of an inhibitory signal of an immune cell and compositions comprising such viruses. The chimeric Newcastle disease viruses and compositions are useful in the treatment of cancer. In addition, described herein are methods for treating cancer comprising administering Newcastle disease viruses in combination with an agonist of a co-stimulatory signal of an immune and/or an antagonist of an inhibitory signal of an immune cell.

Abstract: The present invention relates to methods and compositions for identifying subjects treated with or considered for treatment with checkpoint blockade therapeutic agents that are at higher or lower risk for developing checkpoint therapy associated colitis, by analyzing the intestinal microbiome of those subjects. It is based, at least in part, on the discovery that the abundance of certain intestinal microbiota of the phyla Bacteroidetes, including the bacteria in the families Bacteroidaceae, Rikenellaceae, and Barnesisllaceae, and/or an increase or decrease in microbial genetic pathways involved in polyamine transport and/or B vitamin biosynthesis (e.g., (riboflavin (B2), pantothenate (B5) and thiamine (B1)) are associated with the likelihood of developing checkpoint therapy associated colitis.

Abstract: Described herein are chimeric Newcastle disease viruses engineered to express an agonist of a co-stimulatory signal of an immune cell and compositions comprising such viruses. Also described herein are chimeric Newcastle disease viruses engineered to express an antagonist of an inhibitory signal of an immune cell and compositions comprising such viruses. The chimeric Newcastle disease viruses and compositions are useful in the treatment of cancer. In addition, described herein are methods for treating cancer comprising administering Newcastle disease viruses in combination with an agonist of a co-stimulatory signal of an immune and/or an antagonist of an inhibitory signal of an immune cell.