Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11290
Title: Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™.
Austin 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, Victoria, Australia
Issue Date: 23-Jun-2011
Publication information: 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.
Gov't Doc #: 21698545
URI: https://ahro.austin.org.au/austinjspui/handle/1/11290
DOI: 10.1007/s00262-011-1041-3
Journal: Cancer immunology, immunotherapy : CII
URL: https://pubmed.ncbi.nlm.nih.gov/21698545
Type: Journal Article
Subjects: Adjuvants, Immunologic.administration & dosage
Adult
Aged
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
Down-Regulation
Drug Combinations
Drug Hypersensitivity.etiology.immunology
Female
Humans
Immunohistochemistry
Male
Melanoma.immunology.therapy
Membrane Proteins.administration & dosage.biosynthesis.immunology
Middle Aged
Molecular Sequence Data
Phospholipids.administration & dosage.immunology
Prospective Studies
Saponins.administration & dosage.immunology
Skin.immunology
Appears in Collections:Journal articles

Files in This Item:
File SizeFormat 
21698545.pdf66.11 kBAdobe PDFView/Open
Show full item record

Page view(s)

22
checked on Apr 12, 2024

Download(s)

72
checked on Apr 12, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.