title: Cytotoxicity of human endogenous retrovirus K-specific T cells toward autologous ovarian cancer cells.
abstract: OBJECTIVE
  To determine whether HERV-K envelope (ENV) protein could function as a tumor-associated antigen and elicit specific T-cell responses against autologous ovarian cancer cells.
  
  
  METHODS
  The expression of HERV-K transcripts and ENV protein, the presence of serum antibodies against HERV-K, reverse transcriptase (RT) activities, and cellular immune responses in primary ovarian cancer tissues and patient blood samples were analyzed and compared with samples from patients with benign ovarian diseases and normal female donors.
  
  
  RESULTS
  Ovarian cancer cells in primary tumors and ascites expressed markers of cancer stem cells and markers of both mesenchymal and epithelial cells. Expression of HERV transcripts and HERV-K ENV protein and reverse transcriptase activities were higher in ovarian cancer compared with adjacent normal and benign tissues. The ovarian cancer patient plasma also had high reverse transcriptase activities and the ovarian cancer patient sera contained HERV-K immunoreactive antibodies. HERV-K-specific T cells generated from autologous dendritic cells pulsed with HERV-K ENV antigens exhibited phenotypes and functions consistent with a cellular immune response including T-cell proliferation, IFNγ production, and HERV-K-specific cytotoxic T lymphocyte (CTL) activity. Significantly higher CTL lysis of autologous tumor cells than of uninvolved normal cells was demonstrated in patients with ovarian cancer than patients with benign diseases and further enhanced lysis was observed if T regulatory cells were depleted.
  
  
  CONCLUSIONS
  Endogenous retroviral gene products in ovarian cancer may represent a potentially valuable new pool of tumor-associated antigens for targeting of therapeutic vaccines to ovarian cancer. Clin Cancer Res; 21(2); 471-83. ©2014 AACR.
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas. Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Kiera
authors.initials: K
authors.lastname: Rycaj
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Plummer
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Bingnan
authors.initials: B
authors.lastname: Yin
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. Viral Oncology Program, SRI International, Menlo Park, California. Viral Oncology Program, SRI International, Menlo Park, California.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Garza
authors.affiliation: Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Radvanyi
authors.affiliation: Division of Gynecologic Oncology and Lyndon Baines Johnson Hospital, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Lois M
authors.initials: LM
authors.lastname: Ramondetta
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johanning
authors.affiliation: Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas. Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Dean G
authors.initials: DG
authors.lastname: Tang
authors.affiliation: Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, Texas. Viral Oncology Program, SRI International, Menlo Park, California. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas. feng.wang-johanning@SRI.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang-Johanning
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015686:Gene Products, env / Q000097:blood / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D010051:Ovarian Neoplasms / Q000097:blood* / Q000821:virology; D012194:RNA-Directed DNA Polymerase / Q000097:blood / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: D000951:Antigens, Neoplasm; D015686:Gene Products, env; D012194:RNA-Directed DNA Polymerase