title: Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™.
abstract: BACKGROUND
  NY-ESO-1 protein formulated in ISCOMATRIX™ results in CD4+, CD8+ T cell and antibody-mediated immunity. We evaluated persistence of immunity, relapse-free survival and tumour antigen expression upon relapse in patients vaccinated in an earlier trial.
  
  
  METHODS
  Immunity was measured in 28 patients with resected NY-ESO-1-expressing tumours (melanoma 25, breast 3) 252-1,155 days (median = 681) after vaccination. In the earlier vaccination, trial patients received NY-ESO-1 with ISCOMATRIX™ adjuvant at three protein doses 10 μg, 30 μg or 100 μg (n = 14); 100 μg NY-ESO-1 protein (n = 8) or placebo (n = 6), together with 1 μg of intradermal (ID) NY-ESO-1 protein twice for DTH skin testing. Immune responses assessed in the current study included antibody titres, circulating NY-ESO-1-specific T cells and DTH reactivity 2 days after DTH skin testing with NY-ESO-1 protein (1 μg) or peptides (10 μg). Relapse-free survival was determined for 42 melanoma patients. On relapse NY-ESO-1 and HLA, class I was assessed by immunohistochemistry in 17.
  
  
  RESULTS
  Persisting anti-NY-ESO-1 immunity was detected in 10/14 recipients who had previously received vaccine with ISCOMATRIX™ adjuvant. In contrast, immunity only persisted in 3/14 who received 100 μg un-adjuvanted NY-ESO-1 protein (3/8) or 2 μg DTH protein (0/6) P = 0.02. Hence, persisting NY-ESO-1 immunity was associated with prior adjuvant. Tumour NY-ESO-1 or HLA class I was downregulated in participants who relapsed suggesting immunoediting had occurred.
  
  
  CONCLUSIONS
  Immunoediting suggests that a signal of anti-tumour activity was observed in high-risk resected melanoma patients vaccinated with NY-ESO-1/ISCOMATRIX™. This was associated with measurable persisting immunity in the majority of vaccinated subjects tested. A prospective randomised trial has been undertaken to confirm these results.
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne, Austin Hospital, Heidelberg, VIC, Australia.
authors.forename: Theo
authors.initials: T
authors.lastname: Nicholaou
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Heather M
authors.initials: HM
authors.lastname: Jackson
authors.forename: Nektaria
authors.initials: N
authors.lastname: Dimopoulos
authors.forename: Catherine
authors.initials: C
authors.lastname: Barrow
authors.forename: Judy
authors.initials: J
authors.lastname: Browning
authors.forename: Duncan
authors.initials: D
authors.lastname: Macgregor
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.forename: Wendie
authors.initials: W
authors.lastname: Hopkins
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Ralph
authors.initials: R
authors.lastname: Venhaus
authors.forename: Linda
authors.initials: L
authors.lastname: Pan
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hoffman
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002784:Cholesterol / Q000008:administration & dosage* / Q000276:immunology; D018572:Disease-Free Survival; D015536:Down-Regulation; D004338:Drug Combinations; D004342:Drug Hypersensitivity / Q000209:etiology / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000008:administration & dosage* / Q000276:immunology; D011446:Prospective Studies; D012503:Saponins / Q000008:administration & dosage* / Q000276:immunology; D012867:Skin / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D004338:Drug Combinations; C493786:ISCOMATRIX; D008565:Membrane Proteins; D010743:Phospholipids; D012503:Saponins; D002784:Cholesterol