title: Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma.
abstract: The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 μg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-μg NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4⁺ T-cell responses. CD8⁺ T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8⁺ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4⁺ T-cell responses in the majority of patients; the small proportion of CD8⁺ T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8⁺ T-cell responses.
authors: Cancer Institute, New York University School of Medicine, New York.|Icahn School of Medicine at Mount Sinai Tisch Cancer Institute, Harvard Medical School, New York.
authors: Rachel Lubong
authors: RL
authors: Sabado
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Anna
authors: A
authors: Pavlick
authors: Ludwig Institute for Cancer Research, Harvard Medical School, New York.|Icahn School of Medicine at Mount Sinai Tisch Cancer Institute, Harvard Medical School, New York.
authors: Sacha
authors: S
authors: Gnjatic
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Crystal M
authors: CM
authors: Cruz
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Isabelita
authors: I
authors: Vengco
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Farah
authors: F
authors: Hasan
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Meredith
authors: M
authors: Spadaccia
authors: Department of Pathology, New York University School of Medicine, New York.
authors: Farbod
authors: F
authors: Darvishian
authors: Department of Pathology, New York University School of Medicine, New York.
authors: Luis
authors: L
authors: Chiriboga
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Rose Marie
authors: RM
authors: Holman
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Juliet
authors: J
authors: Escalon
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Caroline
authors: C
authors: Muren
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Crystal
authors: C
authors: Escano
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Ethel
authors: E
authors: Yepes
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Dunbar
authors: D
authors: Sharpe
authors: 3M Drug Delivery Systems Division, Harvard Medical School, New York.
authors: John P
authors: JP
authors: Vasilakos
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Linda
authors: L
authors: Rolnitzsky
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Judith
authors: J
authors: Goldberg
authors: 3M Drug Delivery Systems Division, Harvard Medical School, New York.
authors: John
authors: J
authors: Mandeli
authors: Cancer Institute, New York University School of Medicine, New York.
authors: Sylvia
authors: S
authors: Adams
authors: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York.
authors: Achim
authors: A
authors: Jungbluth
authors: Ludwig Institute for Cancer Research, Harvard Medical School, New York.
authors: Linda
authors: L
authors: Pan
authors: Ludwig Institute for Cancer Research, Harvard Medical School, New York.
authors: Ralph
authors: R
authors: Venhaus
authors: Cancer Institute, New York University School of Medicine, New York.|Dana-Farber Cancer Institute, Harvard Medical School, New York.
authors: Patrick A
authors: PA
authors: Ott
authors: Cancer Institute, New York University School of Medicine, New York.|Department of Pathology, New York University School of Medicine, New York.|Icahn School of Medicine at Mount Sinai Tisch Cancer Institute, Harvard Medical School, New York.
authors: Nina
authors: N
authors: Bhardwaj
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000276:immunology*; D007111:Immunity, Cellular; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives; D008545:Melanoma / Q000628:therapy*; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage; D010446:Peptide Fragments / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D007093:Imidazoles; D008565:Membrane Proteins; D009829:Oleic Acids; D010446:Peptide Fragments; C477385:montanide ISA 51; D008353:Mannitol; C402365:resiquimod
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