IRX-2, a novel in vivo immunotherapeutic, induces maturation and activation of human dendritic cells in vitro.

作者: James E. Egan , Karen J. Quadrini , Frances Santiago-Schwarz , John W. Hadden , Harvey J. Brandwein

DOI: 10.1097/CJI.0B013E3180691593

关键词: CytokineT cellImmunologyCancer researchCD40CD86Antigen-presenting cellHead and neck squamous-cell carcinomaDendritic cellImmunotherapyMedicine

摘要: IRX-2 is a uniform, well-defined set of natural cytokines currently in Phase II clinical trials for squamous cell carcinoma the head and neck (HNSCC). In preliminary studies HNSCC patients, therapy has shown promising results, increasing overall survival patients from 32% to 61% at 48 months. Although it known that specific enhance T activity [e.g., interleukin-2 (IL-2), interferon-gamma, IL-1beta], we chose investigate influence on monocyte-derived dendritic cells (Mo-DCs) isolated human peripheral blood an effort further understand findings. We show here treatment DC resulted morphologic, phenotypic, functional changes consistent with development mature activated DC. Specifically, IRX-2-treated increased expression CD83 CCR7, markers maturation migration, respectively, HLA-DR, CD54, costimulatory molecules CD86 CD40, which are critical mediators activation. Functional induced by included reduced endocytic capacity, ability stimulate IL-12 cytokine production. These results provide plausible mechanistic explanation vivo additional rationale use IRX-2-based immunotherapy patients.

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