title: Results from a phase I clinical study of the novel Ii-Key/HER-2/neu(776-790) hybrid peptide vaccine in patients with prostate cancer.
abstract: OBJECTIVE
  Active immunotherapy is emerging as a potential therapeutic approach for prostate cancer. We conducted the first phase I trial of an Ii-Key/HER-2/neu(776-790) hybrid peptide vaccine (AE37) with recombinant granulocyte macrophage colony-stimulating factor as adjuvant in patients with HER-2/neu(+) prostate cancer. The primary end points of the study were to evaluate toxicity and monitor patients' immune responses to the vaccine.
  
  
  METHODS
  Thirty-two HER-2/neu(+), castrate-sensitive, and castrate-resistant prostate cancer patients were enrolled. Of these, 29 patients completed all six vaccination cycles with AE37. Immunologic responses in the total patient population were monitored by delayed-type hypersensitivity and IFN-gamma ELISPOT and intracellular staining. Regulatory T-cell (Treg) frequency and plasma HER-2/neu and transforming growth factor-beta levels were also determined. Immunologic responses were also analyzed among groups of patients with different clinical characteristics. Local/systemic toxicities were monitored throughout the study.
  
  
  RESULTS
  Toxicities beyond grade 2 were not observed. Seventy-five percent of patients developed augmented immunity to the AE37 vaccine and 65% to the unmodified AE36 peptide as detected in the IFN-gamma-based ELISPOT assay. Intracellular IFN-gamma analyses revealed that AE37 elicited both CD4(+) and CD8(+) T-cell responses. Eighty percent of the patients developed a positive delayed-type hypersensitivity reaction to AE36. Additionally, significant decreases could be detected in circulating Treg frequencies, plasma HER-2/neu, and serum transforming growth factor-beta levels. Patients with less extensive disease developed better immunologic responses on vaccination.
  
  
  CONCLUSIONS
  AE37 vaccine is safe and can induce HER-2/neu-specific cellular immune responses in patients with castrate-sensitive and castrate-resistant prostate cancer, thus emphasizing the potential of AE37 to target HER-2/neu for the immunotherapy of prostate cancer.
authors.affiliation: Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Perez
authors.forename: Nikoletta L
authors.initials: NL
authors.lastname: Kallinteris
authors.forename: Stratos
authors.initials: S
authors.lastname: Bisias
authors.forename: Panagiotis K
authors.initials: PK
authors.lastname: Tzonis
authors.forename: Katerina
authors.initials: K
authors.lastname: Georgakopoulou
authors.forename: Marighoula
authors.initials: M
authors.lastname: Varla-Leftherioti
authors.forename: Michael
authors.initials: M
authors.lastname: Papamichail
authors.forename: Anastasios
authors.initials: A
authors.lastname: Thanos
authors.forename: Eric
authors.initials: E
authors.lastname: von Hofe
authors.forename: Constantin N
authors.initials: CN
authors.lastname: Baxevanis
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011994:Recombinant Proteins; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; C530655:AE37 vaccine; C524355:HER-2 protein (776-790); C121917:T lymphocyte activation molecule H4; C045084:invariant chain