title: The STEAP1(262-270) peptide encapsulated into PLGA microspheres elicits strong cytotoxic T cell immunity in HLA-A*0201 transgenic mice--A new approach to immunotherapy against prostate carcinoma.
abstract: BACKGROUND
  PLGA microsphere-based vaccination has been proven to be effective in immunotherapy of syngeneic model tumors in mice. The critical step for the translation to humans is the identification of immunogenic tumor antigens and potent vaccine formulations to overcome immune tolerance.
  
  
  METHODS
  HLA-A*0201 transgenic mice were immunized with eight different human prostate cancer peptide antigens co-encapsulated with TLR ligands into PLGA microspheres and analyzed for antigen-specific and functional cytotoxic T lymphocyte responses.
  
  
  RESULTS
  Only vaccination with STEAP1(262-270) peptide encapsulated in PLGA MS could effectively crossprime CTLs in vivo. These CTLs recognized STEAP1(262-270) /HLA-A*0201 complexes on human dendritic cells and prostate cancer cell lines and specifically lysed target cells in vivo. Vaccination with PLGA microspheres was much more potent than with incomplete Freund's adjuvant.
  
  
  CONCLUSIONS
  Our data suggests that there exist great differences in the immunogenicity of human PCa peptide antigens despite comparable MHC class I binding characteristics. Immunogenic STEAP1(262-270) peptide encapsulated into PLGA microspheres however was able to induce vigorous and functional antigen-specific CTLs and therefore is a promising novel approach for immunotherapy against advanced stage prostate cancer.
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Herrmann
authors.affiliation: Department of Chemistry, University of Konstanz, Konstanz, Germany.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Wieland
authors.affiliation: Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Legler
authors.affiliation: Department of Chemistry, University of Konstanz, Konstanz, Germany.
authors.forename: Valentin
authors.initials: V
authors.lastname: Wittmann
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.|Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Groettrup
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000494:pharmacology*; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen / Q000235:genetics*; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008863:Microspheres; D010446:Peptide Fragments / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; C514986:STEAP protein (262-270), human
keywords: PLGA microspheres; STEAP; cancer vaccine; prostate cancer; tumor antigen