University of Arkansas

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Bioventures, LLC

Martin J Cannon

Timothy J O'Brien

Alessandro D Santin

Kristina L Bondurant

John Beard

Kazushi Shigemasa

Kellie Kozak Vaidya

Kellie L Kozak

Kellie J Kozak

The invention involves the discovery that if dendritic cells loaded with a tumor antigen are cultured in interleukin-15 (IL-15), or if T cells activated by the dendritic cells are cultured in IL-15, Treg activity that is specific for the tumor antigen is reduced. This reduction in Treg activity results in an increase in anti-tumor immune response. Another embodiment of the invention involves the discovery that incubating dendritic cells with a MAP kinase inhibitor in combination with IL-15 gives synergistic benefits when the dendritic cells are used to activate T cells. Dendritic cell and T cell compositions incubated with IL-15 or a MAP kinase inhibitor are provided.

Inhibition of dendritic cell-driven regulatory T cell activation and potentiation of tumor antigen-specific T cell responses by interleukin-15 and MAP kinase inhibitor

Peptides of from about 7 to about 50 amino acid residues in length that have epitopes that bind to more than one HLA class II protein and stimulate CD4+ T cells for treatment of cancer from one of three serine proteases overexpressed in ovarian cancer and other cancers&#x2014;stratum corneum chymotryptic enzyme, matriptase, and hepsin&#x2014;are described. Since the peptides bind to more than one HLA class II protein variant, they can be used to treat cancer in most patients of a population having a variety of HLA class II alleles. The peptides can be loaded onto autologous dendritic cells of a cancer patient and infused into the patient to activate a CD4+ and CD8+ T cell response that recognizes tumor cells expressing the peptide antigen.

Multi-epitope peptide-loaded dendritic cell immunotherapy for cancer

The present invention discloses the protease stratum corneum chymotrytic enzyme (SCCE) is specifically over-expressed in ovarian and other malignancies. A number of SCCE peptides can induce immune responses to SCCE, thereby demonstrating the potential of these peptides in monitoring and the development of immunotherapies for ovarian and other malignancies.

Immunotherapeutic methods targeted toward stratum corneum chymotryptic enzyme

The present invention discloses the protease stratum corneum chymotryptic enzyme (SCCE) is specifically over-expressed in ovarian and other malignancies. A number of SCCE peptides can induce immune responses to SCCE, thereby demonstrating the potential of these peptides in monitoring and the development of immunotherapies for ovarian and other malignancies.

Methods for the early diagnosis of ovarian cancer

The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. Specifically, the present invention relates to expression of hepsin protease. The detected proteases are themselves specifically over-expressed in certain cancers, and the presence of their genetic precursors may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment.

The invention involves peptides of from about 7 to about 50 amino acid residues in length that have epitopes that bind to more than one HLA class II protein and stimulate CD4+ T cells for treatment of cancer from one of three serine proteases overexpressed in ovarian cancer and other cancers&#x2014;stratum corneum chymotryptic enzyme, matriptase, and hepsin. Since the peptides bind to more than one HLA class II protein variant, they can be used to treat cancer in most patients of a population having a variety of HLA class II alleles. The peptides can be loaded onto autologous dendritic cells of a cancer patient and infused into the patient to activate a CD4+ and CD8+ T cell response that recognizes tumor cells expressing the peptide antigen.

The present invention discloses the protease hepsin is specifically over-expressed in ovarian and other malignancies. A number of hepsin peptides can induce immune responses to hepsin, thereby demonstrating the potential of these peptides in monitoring and the development of immunotherapies for ovarian and other malignancies. There is also provided a hepsin protein variant that is useful as a marker for ovarian cancer cells, prostate cancer cells or kidney cancer cells.

Immunotherapeutic methods targeted towards stratum corneum chymotryptic enzyme

The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. Specifically, the present invention relates to expression of hepsin protease. The detected proteases are themselves specifically overexpressed in certain cancers, and the presence of their genetic precursors may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment.

The disclosed nucleic acid primer sets, used in combination with quantitative amplification (PCR) of tissue cDNA, can indicate the presence of specific proteases in a tissue sample. The detected proteases are themselves specifically overexpressed in certain cancers, and their presence may serve for early detection of associated ovarian and other malignancies, and for the design of interactive therapies for cancer treatment. More specifically, the present invention relates to the uses of stratum corneum chymotrytic enzyme as a marker for ovarian tumor cells.

Growing community of inventors

Little Rock, AR, United States of America

Martin J Cannon