Abstract: This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.

Abstract: The present invention is based, in part, on the discovery that immunotherapy using cell-based tumor cells genetically modified to express heat shock proteins is particularly effective in preventing, prognosing and/or treating cancer (e.g., ovarian cancer). Accordingly, the invention relates to compositions, kits, and methods for preventing, prognosing and/or treating cancer (e.g., ovarian cancer).

Abstract: Nucleic acids encoding a chimeric or fusion polypeptide which polypeptide comprises a first domain comprising a translocation polypeptide; and a second domain comprising at least one antigenic peptide are disclosed. The preferred translocation polypeptide is a bacterial toxin translocation polypeptide, such as domain II of Pseudomonas aeruginosa exotoxin A (ETA(dII)). Such nucleic acids, expression vectors thereof, and cells expressing these vectors are used as vaccine compositions in a method for enhancing an antigen specific immune response, a method of increasing the numbers of CD8+ CTLs specific for a selected desired antigen in a subject, or a method of inhibiting the growth of a tumor in a subject.

Abstract: Methods for treating or preventing recurrence of hyper proliferating diseases, e.g., cancer, are described. A method may comprise priming a mammal by administering to the mammal an effective amount of a nucleic acid composition encoding an antigen or a biologically active homo log thereof and boosting the mammal by administering to the mammal an effective amount of an oncolytic virus comprising a nucleic acid encoding the antigen or the biologically active homolog thereof.

Abstract: Methods for delivering naked DNA vaccines to enhance immune responses, by improving transfection efficiency without safety concerns associated with live viral vectors, are described. A method may comprise administering to a mammalian subject an effective amount of a papillomavirus pseudovirion, wherein the papillomavirus pseudovirion comprises at least one papillomavirus capsid protein encapsidating a naked DNA vaccine, wherein the naked DNA vaccine comprises a first nucleic acid encoding at least one antigen, thereby enhancing the antigen specific immune response relative to administration of the naked DNA vaccine.

Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

Abstract: Nucleic acids encoding a chimeric or fusion polypeptide which polypeptide comprises a first domain comprising a translocation polypeptide; and a second domain comprising at least one antigenic peptide are disclosed. The preferred translocation polypeptide is a bacterial toxin translocation polypeptide, such as domain II of Pseudomonas aeruginosa exotoxin A (ETA(dII)). Such nucleic acids, expression vectors thereof, and cells expressing these vectors are used as vaccine compositions in a method for enhancing an antigen specific immune response, a method of increasing the numbers of CD8+ CTLs specific for a selected desired antigen in a subject, or a method of inhibiting the growth of a tumor in a subject.

Abstract: This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.

Abstract: Methods for treating or preventing hyperproliferating diseases, e.g., cancer, are described. A method may comprise administering to a subject in need thereof a therapeutically effective amount of a chemotherapeutic agent and a DNA vaccine.

Abstract: Novel nucleic acid vectors comprising sequences encoding (a) an antigen, (b) a signal peptide, and (c) a heat shock protein, are disclosed, as are methods for using such vectors to induce antigen-specific immune responses and to treat tumors.

Abstract: The present invention is based, in part, on the discovery that immunotherapy using cell-based tumor cells genetically modified to express heat shock proteins is particularly effective in preventing, prognosing and/or treating cancer (e.g., ovarian cancer). Accordingly, the invention relates to compositions, kits, and methods for preventing, prognosing and/or treating cancer (e.g., ovarian cancer).

Abstract: Improved molecular vaccines comprise nucleic acid vectors that encode a fusion polypeptide that includes polypeptide or peptide physically linked to an antigen. The linked polypeptide is one that (a) promotes processing of the expressed fusion polypeptide via the MHC class I pathway and/or (b) promotes development or activity of antigen presenting cells, primarily dendritic cells. These vaccines employ one of several types of nucleic acid vectors, each with its own relative advantages: naked DNA plasmids, self-replicating RNA replicons and suicidal DNA-based on viral RNA replicons. Administration of such a vaccine results in enhance immune responses, primarily those mediated by CD8+ cytotoxic T lymphocytes, directed against the immunizing antigen part of the fusion polypeptide. Such vaccines are useful against tumor antigens, viral antigens and antigens of other pathogenic microorganisms and can be used in the prevention or treatment of diseases that include cancer and infections.

Abstract: Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

Abstract: This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.

Abstract: Methods for treating or preventing hyperproliferating diseases, e.g., cancer, are described. A method may comprise administering to a subject in need thereof a therapeutically effective amount of a nucleic acid encoding an MHC class I and/or II activator and optionally a nucleic acid encoding an antigen.

Abstract: Superior molecular vaccines comprise nucleic acids, including naked DNA and replicon RNA, that encode a fusion polypeptide that includes an antigenic peptide or polypeptide against which an immune response is desired. Fused to the antigenic peptide is an intercellular spreading protein, in particular a herpes virus protein VP22 or a homologue or functional derivative thereof. Preferred spreading proteins are VP22 from HSV-1 and Marek's disease virus. The nucleic acid can encode any antigenic epitope of interest, preferably an epitope that is processed and presented by MHC class I proteins. Antigens of pathogenic organisms and cells such as tumor cells are preferred. Vaccines comprising HPV-16 E7 oncoprotein are exemplified. Also disclosed are methods of using the vaccines to induce heightened T cell mediated immunity, in particular by cytotoxic T lymphocytes, leading to protection from or treatment of a tumor.

Abstract: Human papillomavirus (HPV) infection is the etiological factor for cervical cancer. Provided are HPV vaccines that generate a humoral immune response to prevent new infection, as well as cell-mediated immunotherapy to eliminate established infection or HPV-related disease. HPV vaccines include nucleic acid sequences encoding HPV16 early proteins E6 and E7. Additional nucleic acid sequences in the vaccines include sequences encoding calreticulin and/or the HPV16 late protein L2. Methods using these vaccines are provided that result in therapeutic effects.

Abstract: Novel nucleic acid vectors comprising sequences encoding (a) calreticulin or a domain thereof, and (b) an antigen, such as human papillomavirus oncoproteins E7 or E6 in detoxified form, are disclosed, as are methods for using such vectors to induce antigen-specific immune responses and to treat or prevent development of tumors.

Abstract: An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and/or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+ T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC's transfected with siRNA targeting Bak and/or Bax serve as improved immunogens and tumor immunotherapeutic agents.

Abstract: This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.