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1.
J Immunother Cancer ; 8(1)2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32317292

RESUMEN

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra el Cáncer/administración & dosificación , Colesterol/administración & dosificación , Melanoma/terapia , Recurrencia Local de Neoplasia/epidemiología , Fosfolípidos/administración & dosificación , Saponinas/administración & dosificación , Neoplasias Cutáneas/terapia , Adyuvantes Inmunológicos/efectos adversos , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/inmunología , Biopsia , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Quimioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante/métodos , Colesterol/efectos adversos , Procedimientos Quirúrgicos Dermatologicos , Supervivencia sin Enfermedad , Método Doble Ciego , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Inmunogenicidad Vacunal , Masculino , Melanoma/diagnóstico , Melanoma/inmunología , Melanoma/mortalidad , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Fosfolípidos/efectos adversos , Saponinas/efectos adversos , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad
2.
Blood ; 113(6): 1257-67, 2009 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-18987360

RESUMEN

Professional antigen-presenting cells (APCs) are sentinel cells of the immune system that present antigen to T lymphocytes and mediate an appropriate immune response. It is therefore surprising that knowledge of the professional APCs in human lymph nodes is limited. Using 3-color immunohistochemistry, we have identified APCs in human lymph nodes, excluding plasmacytoid APCs, that fall into 2 nonoverlapping classes: (1) CD209+ APCs, coexpressing combinations of CD206, CD14, and CD68, that occupied the medullary cords, lined the capsule and trabeculae and were also scattered throughout the diffuse T-lymphocyte areas of the paracortex; and (2) APCs expressing combinations of CD1a, CD207, and CD208, that were always restricted to the paracortex. Surprisingly, this second class of APCs was almost entirely absent from many lymph nodes. Our data suggest that most CD208+ cells, often referred to as "interdigitating cells," derive from migratory APCs, and that the major APC subset consistently resident in the paracortex of human lymph nodes is the CD209+ subset. All APC subsets were demonstrated to be in close contact with the fibroreticular network. The identification of 2 distinct APC populations in the paracortex of human lymph nodes has important implications for understanding T-lymphocyte responses and optimizing vaccine design.


Asunto(s)
Presentación de Antígeno/inmunología , Células Presentadoras de Antígenos/inmunología , Ganglios Linfáticos/inmunología , Antígenos CD/metabolismo , Axila , Células Cultivadas , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas para Inmunoenzimas , Enfermedades Linfáticas , Fenotipo , Piel/citología , Piel/inmunología , Piel/metabolismo , Linfocitos T/inmunología
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