Abstract: Provided are compositions and methods of use thereof that modulate C/EBP homologous stress-related protein (Chop) activity in Myeloid-derived Suppressor Cells (MDSCs). Chop is a key point in the response of MDSCs to tumor-generated stress factors. In turn, the MDSCs release cytokines and other factors that function as immune suppressors, thereby allowing the tumors to thrive and expand. By inhibiting the level of Chop activity, the immunosuppressive function of MDSCs is disrupted. It has also been unexpectedly found that there is a concomitant increase in the ability of MDSCs to act as antigen-presenting and cytokine producing cells so as to act in increasing the efficacy of anti-tumor immune-based therapies.

Abstract: Provided are compositions and methods of use thereof that modulate C/EBP homologous stress-related protein (Chop) activity in Myeloid-derived Suppressor Cells (MDSCs). Chop is a key point in the response of MDSCs to tumor-generated stress factors. In turn, the MDSCs release cytokines and other factors that function as immune suppressors, thereby allowing the tumors to thrive and expand. By inhibiting the level of Chop activity, the immunosuppressive function of MDSCs is disrupted. It has also been unexpectedly found that there is a concomitant increase in the ability of MDSCs to act as antigen-presenting and cytokine producing cells so as to act in increasing the efficacy of anti-tumor immune-based therapies.

Abstract: The present invention provides methods and compositions for modulating an immune response by controlling the level of arginase available to a cell, tissue or system. An immune response can be enhanced or depressed by altering the amount of arginine available to a cell, tissue or system through the manipulation of localized or systemic arginine levels using substances which provide arginine to the body and enzymes which break down arginine, such as arginase and nitric oxide synthase. Increasing or decreasing an immune response according to the present invention provides therapeutic treatments for a variety of conditions and diseases. The present invention also provides clinical methods and kits which can measure the strength or resistance to an immune response in a cell, tissue or system based upon the amount of available arginine and enzymes which break down arginine.

Abstract: A vaccine comprising a liposome preparation including at least one B-cell malignancy-associated antigen, IL-2, alone or in combination with at least one other cytokine, and at least one type of lipid molecule, is useful in a method of inducing humoral and cellular immune responses against malignant B-cells in a mammal.

Abstract: A vaccine comprising a liposome preparation including at least one B-cell malignancy-associated antigen, IL-2, alone or in combination with at least one other cytokine, and at least one type of lipid molecule, is useful in a method of inducing humoral and cellular immune responses against malignant B-cells in a mammal.

Abstract: Methods of identifying a patient having an altered immune status involve determining an immune status index for the patient and comparing it to the immune status index in healthy individuals. In general, an immune status index is the ratio of the amount of a protein that varies significantly in a patient with an altered immune status to the amount of another protein that is substantially invariant in both healthy and immune-altered individuals. Variable proteins can be TCR subunit proteins, T lymphocyte signal transduction pathway proteins, polynucleotide binding proteins or biological response modifiers (BRM).

Abstract: A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels, T lymphocyte signal transduction pathway proteins. These changes provide a method of determining the level of immunosuppression in a mammal by determining the level of expression of at least one selected TCR subunit protein, a protein in the T lymphocyte signal transduction pathway, or of the NF-.kappa.B/rel family and comparing the level and pattern to that found in non-immunosuppressed individuals. The method is useful to identify patients having T lymphocytes capable of activation for immunotherapy and for identifying agents which cause or reverse immunosuppression. An isolated immunosuppressive factor associated with the level of expression of the proteins is useful for suppressing the immune response, for example, in organ transplantation.

Abstract: The present invention provides a liposome comprising an effective immunoadjuvant amount of a lymphokine such as IL-2. Also provided is an effective antineoplastic amount of IL-2 liposomes in combination with adoptively transferred cells stimulated with anti-CD3 monoclonal antibody plus IL-2.

Abstract: Methods of identifying a patient having an altered immune status involve determining an immune status index for the patient and comparing it to the immune status index in healthy individuals. In general, an immune status index is the ratio of the amount of a protein that varies significantly in a patient with an altered immune status to the amount of another protein that is substantially invariant in both healthy and immune-altered individuals. Variable proteins can be TCR subunit proteins, T lymphocyte signal transduction pathway proteins, polynucleotide binding proteins or biological response modifiers (BRM).

Abstract: The present invention provides a liposome comprising an effective immunoadjuvant amount of a lymphokine such as IL-2. Also provided is an effective antineoplastic amount of IL-2 liposomes in combination with adoptively transferred cells stimulated with anti-CD3 monoclonal antibody plus IL-2.

Abstract: A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels and T-lymphocyte signal transduction pathway proteins. These changes provide a method of determining the level of immunosuppression in a mammal by determining the level of expression of at least one selected TCR subunit protein, or a protein in the T lymphocyte signal transduction pathway, and comparing the level to that found in non-immunosuppressed individuals. The method is useful to identify patients having T lymphocytes capable of activation for immunotherapy and for identifying agents which cause or reverse immunosuppression. An isolated immunosuppressive factor associated with the level of expression of the proteins is useful for suppressing the immune response, for example, in organ transplantation.

Abstract: A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels, T lymphocyte signal transduction pathway proteins. These changes provide a method of determining the level of immunosuppression in a mammal by determining the level of expression of at least one selected TCR subunit protein, a protein in the T lymphocyte signal transduction pathway, or of the NF-.kappa.B/rel family and comparing the level and pattern to that found in non-immunosuppressed individuals. The method is useful to identify patients having T lymphocytes capable of activation for immunotherapy and for identifying agents which cause or reverse immunosuppression. An isolated immunosuppressive factor associated with the level of expression of the proteins is useful for suppressing the immune response, for example, in organ transplantation.

Abstract: In accordance with the present invention, a method of culturing lymphocytes is disclosed in which the lymphocytes are cultured in the presence of interleukin-2 (IL-2) and an antibody to a lymphocyte surface receptor, preferably an antibody to a lymphocyte T3 surface receptor. Preferably, the antibody is monoclonal. Cells cultured with anti-CD3 maintain their LAK activity as they increase in number. The cells can also be cultured in the presence of an additional lymphokine to obtain additional LAK activity.Methods of medical treatment are also disclosed in which cells cultured in accordance with the culturing methods of the present invention are introduced into the individual to be treated.

Abstract: The present invention provides a liposome comprising an effective immunoadjuvant amount of a lymphokine such as IL-2. Also provided is an effective antineoplastic amount of IL-2 liposomes in combination with adoptively transferred cells stimulated with anti-CD3 monoclonal antibody plus IL-2.

Abstract: The present invention is directed to a method of increasing the in vivo immune response of lymphocytes by stimulating the lymphocytes in vitro in the presence of an anti-CD3 monoclonal antibody for less than about 24 hours to form stimulated lymphocytes; infusing the stimulated lymphocytes into a tumor-bearing mammal; and administering IL-2 to the mammal. As a result of this method, the anti-CD3 stimulated lymphocytes display enhanced immunotherapeutic, e.g., cytotoxicity or lymphokine production, in vivo as represented by a decrease in the number of tumors by at least about 20%.

Abstract: A method of determining the level of immunosuppression in a mammal involves determining the level of expression of at least one selected TCR subunit protein, or protein in the T lymphocyte signal transduction pathway, and comparing the level to that found in healthy individuals. The method is useful to identify patients having T lymphocytes capable of activation for autologous adoptive immunotherapy and for identifying agents which cause or reverse immunosuppression.