title: Induction of melanoma-associated antigen systemic immunity upon intratumoral delivery of interferon-gamma retroviral vector in melanoma patients.
abstract: A total of 17 patients with metastatic melanoma were treated with intratumoral interferon-gamma (IFN-gamma) retroviral vector in a phase I clinical trial. A cycle of treatment consisted of five daily injections every 2 weeks. Patients were divided into two treatment arms that involved a single course (one cycle) of treatment (group I; n = 9) and multiple cycles (six cycles) of treatment (group II; n = 8). Patients received intratumoral injections of IFN-gamma (10(7) plaque-forming units/mL administered at 0.3, 0.5, and 1.0 mL per cohort of patients). All patients receiving multiple injections either maintained stable disease (n = 5) or achieved a partial or complete response (n = 3) of the injected lesion, whereas in patients receiving a single cycle of treatment, only one of nine patients had a response. Patients were assessed for immunoglobulin G antibody (Ab) responses to the melanoma-associated antigens (MAA) tyrosinase, gp100, TRP-2, and MAGE-A1 by affinity enzyme-linked immunosorbent assay. Anti-MAGE-A1 and tyrosinase Ab were significantly elevated from baseline (day 0) to week 16 during treatment (P = .005; P = .002, respectively) in patients who received multiple injections. Patients undergoing treatment who had a clinical response (stable disease or better) also had significantly more elevated Ab responses to a greater number of MAA (P = .0004). The induction of systemic Ab responses to multiple MAA also correlated with systemic clinical responses. These studies suggest that multiple anti-MAA Ab responses are associated with clinical responses to IFN-gamma retroviral treatment and may be used as surrogate response markers.
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
authors.forename: S
authors.initials: S
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: T C
authors.initials: TC
authors.lastname: Fong
authors.forename: D
authors.initials: D
authors.lastname: Ando
authors.forename: F
authors.initials: F
authors.lastname: Burrows
authors.forename: D J
authors.initials: DJ
authors.lastname: Jolly
authors.forename: J
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: D S
authors.initials: DS
authors.lastname: Hoon
mesh_terms: D000293:Adolescent; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015331:Cohort Studies; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007109:Immunity; D007074:Immunoglobulin G / Q000276:immunology; D007267:Injections / Q000379:methods; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D014442:Monophenol Monooxygenase / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011257:Pregnancy Proteins / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D017931:DNA Primers; D004273:DNA, Neoplasm; D007074:Immunoglobulin G; D007370:Interferon Type I; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D011257:Pregnancy Proteins; D058951:gp100 Melanoma Antigen; C020947:interferon tau; D007371:Interferon-gamma; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase