Abstract: Provided herein are methods for determining the presence of cancer (malignant versus benign), monitoring the progression of cancer, monitoring cancer relapse, monitoring the response to cancer therapy, or cancer staging in a subject, by evaluating CD33+/HLA-DRlow, CD14+/HLA-DRlow, CD66b+/HLA-DRlow or, CD11b+/HLA-DRlow MDSC for activation of a transcription factor. Transcription factors include, but are not limited to, STAT3, pSTAT3, HIF1?, or C/EBP?. The MDSC phenotype can be CD33+HLA-DRlowHIF1?+/STAT3+, CD14+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD66b+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD33+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD11b+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, or CD11b+HLA-DRlowC/EBP?+. Also provided herein are methods for inducing human MDSC from healthy donor peripheral blood mononuclear cells (PBMC) by co-culturing PBMC with human solid tumor cell lines and subsequently measuring their suppressive ability.

Abstract: Provided is an isolated recombinant polypeptide comprising an immunoglobulin domain and a canine OX40L extracellular domain polypeptide fragment or a biological equivalent thereof and compositions comprising: an isolated recombinant polypeptide comprising an immunoglobulin domain and a canine OX40L extracellular domain polypeptide fragment; and a pharmaceutically acceptable carrier. Also provided are methods for treating or ameliorating the symptoms of cancer in a canine comprising administering an effective amount of the isolated recombinant polypeptide of the disclosure and/or a composition of the disclosure to a canine in need thereof.

Abstract: Provided herein are methods for determining the presence of cancer (malignant versus benign), monitoring the progression of cancer, monitoring cancer relapse, monitoring the response to cancer therapy, or cancer staging in a subject, by evaluating CD33+/HLA-DRlow, CD14+/HLA-DRlow, CD66b+/HLA-DRlow or, CD11b+/HLA-DRlow MDSC for activation of a transcription factor. Transcription factors include, but are not limited to, STAT3, pSTAT3, HIF1?, or C/EBP?. The MDSC phenotype can be CD33+HLA-DRlowHIF1?+/STAT3+, CD14+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD66b+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD33+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD11b+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, or CD11b+HLA-DRlowC/EBP?+. Also provided herein are methods for inducing human MDSC from healthy donor peripheral blood mononuclear cells (PBMC) by co-culturing PBMC with human solid tumor cell lines and subsequently measuring their suppressive ability.

Abstract: Provided is a cancer therapeutic agent comprising a cancer targeting molecule linked to a liver-expressed chemokine (LEC). In one embodiment, the cancer targeting molecule is an antibody that targets cancer cells or tumors in vivo. The cancer targeting molecule is associated non-covalently or covalently with LEC. The cancer therapeutic agents of the invention are useful for the treatment of cancer in an individual by reducing the size of a tumor or inhibiting the growth of cancer cells in an individual and/or by inhibiting the development of metastasis. The effectiveness of the therapy using the LEC cancer therapeutic agents can be increased by reducing the activity of immunoregulatory T cells and/or by adoptively transferring immune T cells.

Abstract: Provided is a cancer therapeutic agent comprising a cancer targeting molecule linked to a liver-expressed chemokine (LEC). In one embodiment, the cancer targeting molecule is an antibody that targets cancer cells or tumors in vivo. The cancer targeting molecule is associated non-covalently or covalently with LEC. The cancer therapeutic agents of the invention are useful for the treatment of cancer in an individual by reducing the size of a tumor or inhibiting the growth of cancer cells in an individual and/or by inhibiting the development of metastasis. The effectiveness of the therapy using the LEC cancer therapeutic agents can be increased by reducing the activity of immunoregulatory T cells and/or by adoptively transferring immune T cells.

Abstract: Provided is a cancer therapeutic agent comprising a cancer targeting molecule linked to a liver-expressed chemokine (LEC). In one embodiment, the cancer targeting molecule is an antibody that targets cancer cells or tumors in vivo. The cancer targeting molecule is associated non-covalently or covalently with LEC. The cancer therapeutic agents of the invention are useful for the treatment of cancer in an individual by reducing the size of a tumor or inhibiting the growth of cancer cells in an individual and/or by inhibiting the development of metastasis. The effectiveness of the therapy using the LEC cancer therapeutic agents can be increased by reducing the activity of immunoregulatory T cells and/or by adoptively transferring immune T cells.

Abstract: Provided herein are methods for determining the presence of cancer (malignant versus benign), monitoring the progression of cancer, monitoring cancer relapse, monitoring the response to cancer therapy, or cancer staging in a subject, by evaluating CD33+/HLA-DRlow, CD1430 /HLA-DRlow, CD66b+/HLA-DRlow or, CD11b+/HLA-DRlow MDSC for activation of a transcription factor. Transcription factors include, but are not limited to, STAT3, pSTAT3, HIF1?, or C/EBP?. The MDSC phenotype can be CD33+HLA-DRlowHIF1?+/STAT3+, CD14+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD66b+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD33+HLA-DRlowHIF1?+/STAT3+/pSTAT3+/C/EBPb+, CD11b+HLA-DRlow HIF1?+/STAT3+/pSTAT3+/C/EBPb+, or CD11b+HLA-DRlowC/EBP?+. Also provided herein are methods for inducing human MDSC from healthy donor peripheral blood mononuclear cells (PBMC) by co-culturing PBMC with human solid tumor cell lines and subsequently measuring their suppressive ability.

Abstract: Provided is a cancer therapeutic agent comprising a cancer targeting molecule linked to a CpG oligodeoxynucleotide. Also provided are methods of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or inhibiting the development of metastatic cancer, comprising administering an effective amount of the cancer therapeutic agent. The methods may also include reducing immunoregulatory T cell activity in the individual.

Abstract: Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildtype form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

Abstract: Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildytpe form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

Abstract: Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildytpe form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

Abstract: Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildytpe form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

Abstract: Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildytpe form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

Abstract: Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildtype form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

Abstract: Provided is a cancer therapeutic agent comprising a cancer targeting molecule linked to a liver-expressed chemokine (LEC). In one embodiment, the cancer targeting molecule is an antibody that targets cancer cells or tumors in vivo. The cancer targeting molecule is associated non-covalently or covalently with LEC. The cancer therapeutic agents of the invention are useful for the treatment of cancer in an individual by reducing the size of a tumor or inhibiting the growth of cancer cells in an individual and/or by inhibiting the development of metastasis. The effectiveness of the therapy using the LEC cancer therapeutic agents can be increased by reducing the activity of immunoregulatory T cells and/or by adoptively transferring immune T cells.

Abstract: A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.

Abstract: A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.

Abstract: Liposomal conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.

Abstract: Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildtype form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.

Abstract: Liposomal conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.