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Title: Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™.
Authors: Nicholaou, Theo;Chen, Weisan;Davis, Ian D;Jackson, Heather M;Dimopoulos, Nektaria;Barrow, Catherine;Browning, Judy;Macgregor, Duncan;Williams, David;Hopkins, Wendie;Maraskovsky, Eugene;Venhaus, Ralph;Pan, Linda;Hoffman, Eric W;Old, Lloyd J;Cebon, Jonathan S
Affiliation: Ludwig Institute for Cancer Research, Melbourne, Austin Hospital, Heidelberg, VIC, Australia
Issue Date: 23-Jun-2011
Citation: Cancer Immunology, Immunotherapy : Cii 2011; 60(11): 1625-37
Abstract: 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.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.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.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.
Internal ID Number: 21698545
DOI: 10.1007/s00262-011-1041-3
Type: Journal Article
Subjects: Adjuvants, Immunologic.administration & dosage
Amino Acid Sequence
Antigens, Neoplasm.administration & dosage.biosynthesis.immunology
Breast Neoplasms.immunology.therapy
Cancer Vaccines.administration & dosage.immunology
Cholesterol.administration & dosage.immunology
Disease-Free Survival
Drug Combinations
Drug Hypersensitivity.etiology.immunology
Membrane Proteins.administration & dosage.biosynthesis.immunology
Middle Aged
Molecular Sequence Data
Phospholipids.administration & dosage.immunology
Prospective Studies
Saponins.administration & dosage.immunology
Appears in Collections:Journal articles

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