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01.11.2011 | Original article

Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™

verfasst von: Theo Nicholaou, Weisan Chen, Ian D. Davis, Heather M. Jackson, Nektaria Dimopoulos, Catherine Barrow, Judy Browning, Duncan MacGregor, David Williams, Wendie Hopkins, Eugene Maraskovsky, Ralph Venhaus, Linda Pan, Eric W. Hoffman, Lloyd J. Old, Jonathan Cebon

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2011

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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.

Conclusion

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.

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Titel: Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™
verfasst von: Theo Nicholaou
Weisan Chen
Ian D. Davis
Heather M. Jackson
Nektaria Dimopoulos
Catherine Barrow
Judy Browning
Duncan MacGregor
David Williams
Wendie Hopkins
Eugene Maraskovsky
Ralph Venhaus
Linda Pan
Eric W. Hoffman
Lloyd J. Old
Jonathan Cebon
Publikationsdatum: 01.11.2011
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2011
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1041-3

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Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™

Abstract

Background

Methods

Results

Conclusion

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