University of California

Gale Arthur Granger

Tetsuya Gatanaga

John C Hiserodt

Martin R Graf

James A Thompson

James F Thompson

Robert S Yamamoto

The biological effects of the cytokine TNF are mediated by binding to receptors on the surface of cells. This disclosure describes new proteins and polynucleotides that promote enzymatic cleavage and release of TNF receptors. Also provided are methods for identifying additional compounds that influence TNF receptor shedding. As the active ingredient in a pharmaceutical composition, the products of this invention increase or decrease TNF signal transduction, thereby alleviating the pathology of disease.

Pharmaceutical compositions for treating arthritis and inflammatory disease

This invention comprises cellular vaccines and methods of using them in cancer immunotherapy, particularly in humans. The vaccines comprise a source of tumor-associated antigen, and a cytokine-secreting cell line. Tumor antigen may be provided in the form of primary tumor cells, tumor cell lines or tumor extracts prepared from the subject. In certain embodiments of the invention, the cytokine-secreting line is a separate tumor line that is allogeneic to the patient and genetically altered so as to produce a cytokine at an elevated level. Exemplary cytokines are IL-4, GM-CSF, IL-2, TNF-&#x3b1;, and M-CSF in the secreted or membrane-bound form. In these embodiments, the cytokine-producing cells provide immunostimulation in trans to generate a specific immune response against the tumor antigen. Vaccines may be tailored for each type of cancer or for each subject by mixing tumor antigen with a favorable number of cytokine-producing cells, or with a cocktail of such cells producing a plurality of cytokines at a favorable ratio.

Pharmaceutical composition for cancer treatment containing cells that express a membrane cytokine

This invention provides methods and compositions for treating tumors. The cell population is made up of alloactivated lymphocytes from the patient or from one or more third-party donors that are alloactivated in a mixed lymphocyte culture. It can be placed into the tumor bed, or combined with tumor-associated antigen for administration to a distal site as a vaccine. The compositions recruit activated participation of the host Immune system, which then reacts against the tumor and provides a level of ongoing protection. Employing multiple third party donor cells confers particular advantages in terms of effectiveness, timing, and ease of use.

Treating tumors using implants comprising combinations of allogeneic cells

Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokline

The biological effects of the cytokine TNF are mediated by binding to receptors on the surface of cells. This disclosure describes new proteins and polynucleotides that promote enzymatic cleavage and release of TNF receptors. Also provided are method for identifying additional compounds that influence TNF receptor shedding. As the active ingredient in a pharmaceutical composition, the products of this invention increase or decrease TNF signal transduction, thereby alleviating the pathology of disease.

Method for producing TNF receptor releasing enzyme

Treating arthritis with TNF receptor releasing enzyme

Screening for drugs that affect TNF receptor releasing enzyme

The present invention relates to methods of regulating TNF activity indirectly by regulating the activity or concentration of TNF receptor releasing enzyme (TRRE). Preferably, the TRRE activity is regulated local to the site of the condition to be treated. In the case of diseases associated with elevated levels of TNF, such as rheumatoid arthritis, TRRE is administered to the site of inflammation in an amount sufficient to decrease the local levels of TNF. In the case of diseases, such as cancer, that benefit from increased levels of TNF, the level of TRRE is decreased at the disease site.

System for discovering and producing polypeptides that cause TNF receptor shedding

The present invention relates to methods of regulating TNF receptor releasing enzyme (TRRE) activity. Composition altering TRRE activity, including a family of proteins and the genes encoding these proteins having TRRE activity, are provided. These proteins, RNA products, or DNA sequences can be administered to individuals suffering from a disease characterized by abnormal TRRE activity. In the case of diseases associated with elevated levels of TNF, such as rheumatoid arthritis, an inhibitor of TRRE is administered to the disease site to decrease the local levels of TNF. Methods of isolating other compositons which increase or decrease TRRE activity are also provided.

Tumor necrosis factor receptor releasing enzyme

Method for obtaining modulators of TNF receptor releasing enzyme

Native TNF receptor releasing enzyme

This invention comprises cellular vaccines and methods of using them in cancer immunotherapy, particularly in humans. The vaccines comprise a source of tumor-associated antigen, and a cytokine-secreting cell line. Tumor antigen may be provided in the form of primary tumor cells, tumor cell lines or tumor extracts prepared from the subject. In certain embodiments of the invention, the cytokine-secreting line is a separate tumor line that is allogeneic to the patient and genetically altered so as to produce a cytokine at an elevated level. Exemplary cytokines are IL-4, GM-CSF, IL-2, TNF-&agr;, and M-CSF in the secreted or membrane-bound form. In these embodiments, the cytokine-producing cells provide immunostimulation in trans to generate a specific immune response against the tumor antigen. Vaccines may be tailored for each type of cancer or for each subject by mixing tumor antigen with a favorable number of cytokine-producing cells, or with a cocktail of such cells producing a plurality of cytokines at a favorable ratio.

Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokine

This invention comprises cellular vaccines and methods of using them in cancer immunotherapy, particularly in humans. The vaccines comprise stimulated lymphocytes allogeneic to the subject being treated, along with a source of tumor-associated antigen. The allogeneic lymphocytes can be stimulated by combining or coculturing them with leukocytes obtained from the subject to be treated or from another third-party donor. Tumor antigen may be provided in the form of primary tumor cells, tumor cell lines or tumor extracts prepared from the subject. Stimulated allogeneic lymphocytes and tumor antigen are combined and administered at a site distant from the primary tumor, in order to prime or boost a systemic cellular anti-tumor immune response. This approach overcomes the natural refractory nature of the immune system to stimulation by tumor antigens, generating a host response and potentially improving the clinical outcome.

Cancer immunotherapy using tumor cells combined with mixed lymphocytes

This invention provides methods and compositions for treating tumors by implanting near the tumor an alloactivated cell population. The cell population is made up of a plurality of third-party donor cells that have been cultured together ex vivo, and harvested near the time of peak cytokine secretion. Once placed in the tumor bed, the alloactivated cells recruit active participation of the host, which then reacts against the tumor and provides a level of ongoing protection. Employing multiple third party donor cells confers particular advantages in terms of effectiveness, timing, and ease of use.

Growing community of inventors

Laguna Beach, CA, United States of America

Gale Arthur Granger