Tumor-Associated Antigen

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Rimas J Orentas - One of the best experts on this subject based on the ideXlab platform.

  • Serum from mice immunized in the context of Treg inhibition identifies DEK as a neuroblastoma tumor Antigen
    BMC Immunology, 2007
    Co-Authors: Jin Zheng, M Eric Kohler, Qingrong Chen, James Weber, Javed Khan, Bryon D Johnson, Rimas J Orentas
    Abstract:

    Background We have developed a cell-based vaccine that features the expression of both CD80 and CD86 on the surface of a murine neuroblastoma cell line. The cellular immunity induced by this vaccine is enhanced by treatment with antibody that interferes with T-regulatory cell (Treg) function and we report here that immunization combined with interfering with Treg function also produces a profound serological effect. Serum from mice immunized with our cell-based vaccine in the context of Treg blockade was used to screen a cDNA expression library constructed from the parental neuroblastoma tumor cell line, AGN2a. Results Serum from mice vaccinated in the context of Treg blockade identified a number of potentially oncogenic transcripts that may serve as important immune targets in a tumor-derived cDNA library screen. This novel approach identified far more candidates than could be seen with serum derived from vaccine-treated only, Treg-depleted only, or tumor-bearing mice. The most commonly identified Tumor-Associated Antigen, using serum from immunized and Treg-depleted mice, was the DEK oncogene. Altered expression of the DEK oncogene has been implicated in a number of human cancers. Importantly, we were able to demonstrate that the DEK oncogene also induces a T cell response. Conclusion The use of post-vaccine immune serum in this report differs from previous approaches where serum collected at the time of cancer onset or diagnosis and was used for tumor Antigen identification. We hypothesize that the use of diagnostic serum samples may be inadequate for the clinical translation of this approach, and that identification of protective immunogenic tumor Antigens may require the use of serum from post-treatment or vaccinated subjects. The identification of DEK as a Tumor-Associated Antigen capable of eliciting a T cell response validates our experimental approach and argues for the Antigens we have identified here to be evaluated as targets of effector immunity and as vaccine candidates.

David T. Curiel - One of the best experts on this subject based on the ideXlab platform.

  • Selective induction of Tumor-Associated Antigens in murine pulmonary vasculature using double-targeted adenoviral vectors
    Gene Therapy, 2005
    Co-Authors: Maaike Everts, Sangae Kim-park, Meredith A. Preuss, Michael J. Passineau, Joel N. Glasgow, Alexander Pereboev, Parameshwar J. Mahasreshti, William E. Grizzle, Paul N. Reynolds, David T. Curiel
    Abstract:

    Targeted therapies directed to Tumor-Associated Antigens are being investigated for the treatment of cancer. However, there are few suitable animal models for testing the ability to target these tumor markers. Therefore, we have exploited mice transgenic for the human coxsackie and adenovirus receptor (hCAR) to establish a new model for transient expression of human Tumor-Associated Antigens in the pulmonary vasculature. Systemic administration of Ad in hCAR mice resulted in an increase in transgene expression in the lungs compared to wild-type mice, as determined using a luciferase reporter gene. To reduce transgene expression in the liver, the predominant organ of ectopic Ad localization and transgene expression following systemic administration, we utilized the endothelial-specific flt-1 promoter, which resulted in a further increased lung-to-liver ratio of luciferase expression. Administration of an adenoviral vector encoding the Tumor-Associated Antigen carcinoembryonic Antigen (CEA) under transcriptional control of the flt-1 promoter resulted in selective expression of this Antigen in the pulmonary vasculature of hCAR mice. Feasibility of targeting to expressed CEA was subsequently demonstrated using adenoviral vectors preincubated with a bifunctional adapter molecule recognizing this Tumor-Associated Antigen, thus demonstrating utility of this transient transgenic animal model.

  • 1017. Selective Induction of Tumor-Associated Antigens in Murine Pulmonary Vasculature Using Double-Targeted Adenoviral Vectors
    Molecular Therapy, 2005
    Co-Authors: Maaike Everts, Sangae Kim-park, Meredith A. Preuss, Michael J. Passineau, Joel N. Glasgow, Alexander Pereboev, Parameshwar J. Mahasreshti, William E. Grizzle, Paul N. Reynolds, David T. Curiel
    Abstract:

    Targeted therapies directed to Tumor-Associated Antigens are being investigated for the treatment of cancer. However, there are few suitable animal models for testing the ability to target these tumor markers. Therefore, we have exploited mice transgenic for the human coxsackie and adenovirus receptor (hCAR) to establish a new model for transient expression of human Tumor-Associated Antigens in the pulmonary vasculature. Systemic administration of Ad in hCAR mice resulted in an increase in transgene expression in the lungs compared to wild type mice, as determined using a luciferase reporter gene. To reduce transgene expression in the liver, the predominant organ of ectopic Ad localization and transgene expression following systemic administration, we utilized the endothelial-specific flt-1 promoter, which resulted in a further increased lung-to-liver ratio of luciferase expression. Administration of an adenoviral vector encoding the Tumor-Associated Antigen carcinoembryonic Antigen (CEA) under transcriptional control of the flt-1 promoter resulted in selective expression of this Antigen in the pulmonary vasculature of hCAR mice. Feasibility of targeting to expressed CEA was subsequently demonstrated using adenoviral vectors pre-incubated with a bifunctional adapter molecule recognizing this Tumor-Associated Antigen, thus demonstrating utility of this transient transgenic animal model.

Nicholas P Restifo - One of the best experts on this subject based on the ideXlab platform.

  • active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus encoding a model tumor associated Antigen
    Journal of Immunology, 1995
    Co-Authors: Michael Wang, Vincenzo Bronte, Pauline W Chen, Linda Gritz, Dennis Panicali, Steven A Rosenberg, Nicholas P Restifo
    Abstract:

    Some tumor cells express Ags that are potentially recognizable by T lymphocytes and yet do not elicit significant immune responses. To explore new immunotherapeutic strategies aimed at enhancing the recognition of these Tumor-Associated Ags (TAA), we developed an experimental mouse model consisting of a lethal clone of the BALB/c tumor line CT26 designated CT26.WT, which was transduced with the lacZ gene encoding beta-galactosidase, to create CT26.CL25. The growth rate and lethality of CT26.CL25 and CT26.WT were virtually identical despite the expression by CT26.CL25 of the model tumor Ag in vivo. A recombinant fowlpox virus (rFPV), which is replication incompetent in mammalian cells, was constructed that expressed the model TAA, beta-galactosidase, under the influence of the 40-kDa vaccinia virus early/late promoter. This recombinant, FPV.bg40k, functioned effectively in vivo as an immunogen, eliciting CD8+ T cells that could effectively lyse CT26.CL25 in vitro. FPV.bg40k protected mice from both subcutaneous and intravenous tumor challenge by CT26.CL25, and most surprisingly, mice bearing established 3-day pulmonary metastasis were found to have significant, Ag-specific decreases in tumor burden and prolonged survival after treatment with the rFPV. These observations constitute the first reported use of rFPV in the prevention and treatment of an experimental cancer and suggest that changing the context in which the immune system encounters a TAA can significantly and therapeutically alter the host immune response against cancer.

Jin Zheng - One of the best experts on this subject based on the ideXlab platform.

  • Serum from mice immunized in the context of Treg inhibition identifies DEK as a neuroblastoma tumor Antigen
    BMC Immunology, 2007
    Co-Authors: Jin Zheng, M Eric Kohler, Qingrong Chen, James Weber, Javed Khan, Bryon D Johnson, Rimas J Orentas
    Abstract:

    Background We have developed a cell-based vaccine that features the expression of both CD80 and CD86 on the surface of a murine neuroblastoma cell line. The cellular immunity induced by this vaccine is enhanced by treatment with antibody that interferes with T-regulatory cell (Treg) function and we report here that immunization combined with interfering with Treg function also produces a profound serological effect. Serum from mice immunized with our cell-based vaccine in the context of Treg blockade was used to screen a cDNA expression library constructed from the parental neuroblastoma tumor cell line, AGN2a. Results Serum from mice vaccinated in the context of Treg blockade identified a number of potentially oncogenic transcripts that may serve as important immune targets in a tumor-derived cDNA library screen. This novel approach identified far more candidates than could be seen with serum derived from vaccine-treated only, Treg-depleted only, or tumor-bearing mice. The most commonly identified Tumor-Associated Antigen, using serum from immunized and Treg-depleted mice, was the DEK oncogene. Altered expression of the DEK oncogene has been implicated in a number of human cancers. Importantly, we were able to demonstrate that the DEK oncogene also induces a T cell response. Conclusion The use of post-vaccine immune serum in this report differs from previous approaches where serum collected at the time of cancer onset or diagnosis and was used for tumor Antigen identification. We hypothesize that the use of diagnostic serum samples may be inadequate for the clinical translation of this approach, and that identification of protective immunogenic tumor Antigens may require the use of serum from post-treatment or vaccinated subjects. The identification of DEK as a Tumor-Associated Antigen capable of eliciting a T cell response validates our experimental approach and argues for the Antigens we have identified here to be evaluated as targets of effector immunity and as vaccine candidates.

Shuren Zhang - One of the best experts on this subject based on the ideXlab platform.