title: Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients.
abstract: OBJECTIVE
  Long peptides are efficiently presented to both CD4(+) and CD8(+) T cells after intracellular processing by antigen-presenting cells. To investigate the safety and in vivo immunogenicity of synthetic overlapping long peptides (OLP) from a human tumor self-antigen, we conducted a phase I clinical trial with OLP from cancer-testis antigen NY-ESO-1 in various adjuvant combinations.
  
  
  METHODS
  Twenty-eight patients with advanced ovarian cancer in second or third remission were enrolled sequentially in three cohorts and received at least one vaccination. Patients in Cohort 1 (n = 4) received 1.0 mg OLP, Cohort 2 (n = 13) received OLP in Montanide-ISA-51, and Cohort 3 (n = 11) received OLP + 1.4 mg Poly-ICLC in Montanide-ISA-51 on weeks 1, 4, 7, 10, and 13. Humoral and cellular responses were evaluated by standardized immunomonitoring techniques (ELISA, ELISPOT assay, intracellular cytokine staining, and tetramer staining).
  
  
  RESULTS
  The vaccine was generally well tolerated with injection site reactions and fatigue that resolved. NY-ESO-1-specific antibody and CD8(+) T cells were undetectable after vaccination with OLP alone, but were found in 6 of 13 (46%) and 8 of 13 (62%) patients, respectively, after vaccination with OLP+Montanide, and in 10 of 11 (91%) and 10 of 11 (91%) patients, respectively, after vaccination with OLP+Montanide+Poly-ICLC. NY-ESO-1-specific CD4(+) T cells were detected in all patients with greater frequency and polyclonality when Montanide-ISA-51 was used for vaccination. Inclusion of Poly-ICLC as an adjuvant further accelerated the induction of NY-ESO-1-specific immune responses.
  
  
  CONCLUSIONS
  The current study shows that NY-ESO-1 OLP vaccine is safe and rapidly induces consistent integrated immune responses (antibody, CD8(+) and CD4(+)) in nearly all vaccinated patients when given with appropriate adjuvants.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Takemasa
authors.initials: T
authors.lastname: Tsuji
authors.forename: Luis
authors.initials: L
authors.lastname: Ferran
authors.forename: Erika
authors.initials: E
authors.lastname: Ritter
authors.forename: Christine
authors.initials: C
authors.lastname: Sedrak
authors.forename: Kevin
authors.initials: K
authors.lastname: Tuballes
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.forename: Katherine
authors.initials: K
authors.lastname: Bell-McGuinn
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.forename: Jason
authors.initials: J
authors.lastname: Konner
authors.forename: William
authors.initials: W
authors.lastname: Tew
authors.forename: David R
authors.initials: DR
authors.lastname: Spriggs
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hoffman
authors.forename: Ralph
authors.initials: R
authors.lastname: Venhaus
authors.forename: Linda
authors.initials: L
authors.lastname: Pan
authors.forename: Andres M
authors.initials: AM
authors.lastname: Salazar
authors.forename: Catherine Magid
authors.initials: CM
authors.lastname: Diefenbach
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D056724:Immunity, Humoral; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D010455:Peptides; D022223:Vaccines, Subunit; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C