title: NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus.
abstract: Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8(+) or CD4(+) T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4(+) T cell and antibody response, which was maintained by both regiments at similar levels. However, CD8(+) T cell responses were significantly boosted in 3 out of 18 patients in Arm A after the first rF-NY-ESO-1 injection and such responses were maintained until the end of the trial, while no patients in Arm B showed similar CD8(+) T cell responses. In addition, our results clearly identified immunodominant regions in the NY-ESO-1 protein: NY-ESO-179-102 and NY-ESO-1115-138 for CD4+ T cells and NY-ESO-185-108 for CD8+ T cells in a large proportion of vaccinated patients. These regions of NY-ESO-1 protein should be considered in future clinical trials as immunodominant epitopes.
authors: Radcliffe Department of Medicine, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DU, United Kingdom.
authors: Ji-Li
authors: JL
authors: Chen
authors: Amina
authors: A
authors: Dawoodji
authors: Andrea
authors: A
authors: Tarlton
authors: Sacha
authors: S
authors: Gnjatic
authors: Abdelouahid
authors: A
authors: Tajar
authors: Ioannis
authors: I
authors: Karydis
authors: Judy
authors: J
authors: Browning
authors: Sarah
authors: S
authors: Pratap
authors: Christian
authors: C
authors: Verfaille
authors: Ralph R
authors: RR
authors: Venhaus
authors: Linda
authors: L
authors: Pan
authors: Douglas G
authors: DG
authors: Altman
authors: Jonathan S
authors: JS
authors: Cebon
authors: Lloyd L
authors: LL
authors: Old
authors: Paul
authors: P
authors: Nathan
authors: Christian
authors: C
authors: Ottensmeier
authors: Mark
authors: M
authors: Middleton
authors: Vincenzo
authors: V
authors: Cerundolo
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002784:Cholesterol / Q000494:pharmacology*; D004338:Drug Combinations; D005587:Fowlpox virus / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D010743:Phospholipids / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D004338:Drug Combinations; C493786:ISCOMATRIX; D008565:Membrane Proteins; D010743:Phospholipids; D012503:Saponins; D014614:Vaccines, Synthetic; D002784:Cholesterol
keywords: Fowlpox; ISCOMATRIX; NY-ESO-1; cancer vaccines