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• W122948020 abstract "Interleukin (IL)-21, the lastly discovered member of the IL-2 family, is a pleiotropic cytokine produced by CD4+ T cells. IL-21 has shown anti-tumour activity in several pre-clinical tumour models. In addition, clinical phase I-II trials have shown that IL-21 has an acceptable toxicity and induces immune-activation resulting in some clinical responses in patients with metastatic melanoma and renal carcinoma. Stage 4 neuroblastoma (NB) is frequently an incurable disease and it is assumed that immunotherapy (IT) may complement existing treatments. We developed a syngeneic mouse model of Neuro2a NB resembling human stage 4 disease to test different therapies. IT with a cellular vaccine consisting of IL-21-transduced NB cells (Neuro2a/IL-21) cured about one third of syngeneic mice bearing disseminated NB, through a CD8+ T cell-dependent response. NB may induce immune-regulatory mechanisms, which may limit the efficacy of IT. The co-administration of an anti-CD25 monoclonal antibody (mAb), targeting immune-suppressive CD4+CD25+FoxP3+ regulatory T (Treg) cells, slightly augmented the efficacy of IL-21-based IT. However, an anti-CD4 mAb combined with the vaccine produced an even higher cure rate (80%). The potent synergistic effect achieved by the anti-CD4 mAb was related to a complete depletion of CD4+CD25+FoxP3+ Treg cells and possibly of other tumour-conditioned CD4+ T cell subsets. Mice receiving the IL-21-releasing vaccine+anti-CD4 mAb recovered their CD4+ T cell counts in 90 days and developed immunity to NB. Preliminary data indicate that the administration of recombinant (r) IL-21 may have limited effects but that anti-CD4 mAb co-treatment strongly augmented IL-21 IT. These data open new perspectives for the use of IL-21-based immunotherapy in conjunction with CD4+ lymphodepletion in human stage 4 NB." @default.
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• W122948020 date "2011-10-03" @default.
• W122948020 modified "2023-09-23" @default.
• W122948020 title "Neuroblastoma: Perspectives for the Use of IL-21 in Immunotherapy" @default.
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• W122948020 doi "https://doi.org/10.1007/978-94-007-2418-1_12" @default.
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