Abstract: Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a specific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.

Abstract: Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a specific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.

Abstract: Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a specific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.

Abstract: The invention features new helper virus-free methods for making herpesvirus amplicon particles that can be used in immunotherapies, including those for treating any number of infectious diseases and cancers (including chronic lymphocytic leukemia, other cancers in which blood cells become malignant, lymphomas (e.g. Hodgkin's lymphoma or non-Hodgkin's type lymphomas). Described herein are methods of making helper virus-free HSV amplicon particles; cells that contain those particles (e.g., packaging cell lines or patients' cells, infected in vivo or ex vivo); particles produced according to those methods; and methods of treating a patient with an hf-HSV particle made according to those methods.

Abstract: Cell-based immunotherapy (e.g., immunization or vaccination) may be improved by frequent administration to a human subject of allogeneic cancer cells secreting a modified heat shock protein (e.g., gp96), depletion of B cells in the subject, or both. Antigen (e.g., epitope derived from neoantigen or tumor antigen of allogeneic or syngeneic cancer cells) may induce a specific immune response in the subject. For example, the epitope bound in an immunogenic complex with the secreted heat shock protein may be obtained from allogeneic cancer cells coexpressing both secreted gp96 and antigen, or from syngeneic cancer cells of the subject expressing only antigen.

Abstract: An analogous vaccine to tumor cells is produced by transducing the tumor cells with a herpes simplex virus amplicon containing the gene for an immunomodulatory protein to provide transient expression of the immunomodulatory protein by the cells. The tumor cells may transduced with the herpes simplex amplicons ex vivo or in vivo. Suitable immunomodulatory proteins include cytokines, for example, interleukins, interferons, and chemokines such as RANTES; intercellular adhesion molecules, for example ICAM-1 and costimulatory factors such as B7.1. The tumor cells may also be transduced with one or more species of amplicon containing genes for two or more different immunomodulatory proteins.

Abstract: An autologous vaccine to tumor cells is produced by transducing the tumor cells with a herpes virus amplicon containing the gene for an immunomodulatory protein to provide transient expression of the immunomodulatory protein by the cells. The tumor cells may transduced with the herpes simplex amplicons ex vivo or in vivo. Suitable immunomodulatory proteins include cytokines, for example, interleukins, interferons, and chemokines such as RANTES, intercellular adhesion molecules, for example ICAM-1 and costimulatory factors such as B7.1. The tumor cells may also be transduced with one or more species of amplicon containing genes for two or more different immunomodulatory proteins.

Abstract: The present invention relates to chimeric molecules for the stimulation of an anti-tumor immune response to facilitate immune eradication of breast, ovarian and other cancer cells. The chimeric molecules include a binding region which specifically binds to a tumor specific antigen and a chemokine and/or costimulatory ligand. The invention further provides methods for inducing a tumor specific immune response and compositions which can be administered to mammals.

Abstract: The invention features new helper virus-free methods for making herpesvirus amplicon particles that can be used in immunotherapies, including those for treating any number of infectious diseases and cancers (including chronic lymphocytic leukemia, other cancers in which blood cells become malignant, lymphomas (e.g. Hodgkin's lymphoma or non-Hodgkin's type lymphomas). Described herein are methods of making helper virus-free HSV amplicon particles; cells that contain those particles (e.g., packaging cell lines or patients'cells, infected in vivo or ex vivo); particles produced according to those methods; and methods of treating a patient with an hf-HSV particle made according to those methods.

Abstract: The present invention relates generally to a novel human T-cell lymphotropic, or leukemia, virus type II (HTLV-II) isolate designated NRA. HTLV-IINRA was originally isolated from a patient with atypical hairy cell leukemia. Preliminary restriction analysis of this isolate demonstrated that it differs genetically from the prototypical HTLV-II isolate Mo. HTLV-IINRA proviral molecular clones were obtained and the entire nucleotide sequence of the virus ascertained. The claimed invention is particularly directed toward the gp46 and p21e envelope proteins encoded by the env gene. Methods and kits for the detection of HTLV-II antibodies employing these envelope proteins are also described.

Abstract: Modified tRNA molecules are provided which inhibit HIV-1 replication. A tRNA molecule has a modified aminoacyl acceptor stem with a 3′ segment which has reduced complementarity to the HIV primer binding site can initiate aberrant reverse transcription and/or interfere with reverse transcription. tRNA molecules which are modified in regions outside the acceptor stem which interact with reverse trancriptase or the HIV-1 RNA template can also inhibit HIV-1 replication. Methods are disclosed for introducing the modified tRNA molecules into human cells.

Abstract: Methods for treating a mammal with lymphoma using a combination of interleukin-2 (IL-2) or variant thereof and at least one anti-CD20 antibody or fragment thereof are provided. These anti-tumor agents are administered as two separate pharmaceutical compositions, one containing IL-2 (or variant thereof), the other containing at least one anti-CD20 antibody (or fragment thereof), according to a dosing regimen. Administering of these two agents together potentiates the effectiveness of either agent alone, resulting in a positive therapeutic response that is improved with respect to that observed with either agent alone. The anti-tumor effects of these agents can be achieved using lower dosages of IL-2, thereby lessening the toxicity of prolonged IL-2 administration and the potential for tumor escape.

Abstract: An autologous vaccine to tumor cells is produced by transducing the tumor cells with a herpes simplex virus amplicon containing the gene for an immunomodulatory protein to provide transient expression of the immunomodulatory protein by the cells. The tumor cells may transduced with the herpes simplex amplicons ex vivo or in vivo. Suitable immunomodulatory proteins include cytokines, for example, interleukins, interferons, and chemokines such as RANTES; intercellular adhesion molecules, for example ICAM-1 and costimulatory factors such as B7.1. The tumor cells may also be transduced with one or more species of amplicon containing genes for two or more different immunomodulatory proteins.