Neuroblastoma: Perspectives for the Use of IL-21 in Immunotherapy

摘要: Interleukin (IL)-21, the lastly discovered member of 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 that an acceptable toxicity and induces immune-activation resulting some responses patients with metastatic melanoma renal carcinoma. Stage 4 neuroblastoma (NB) frequently incurable disease it assumed immunotherapy (IT) may complement existing treatments. We developed syngeneic mouse model Neuro2a NB resembling human stage to test different therapies. IT cellular vaccine consisting IL-21-transduced cells (Neuro2a/IL-21) cured about one third mice bearing disseminated NB, through CD8+ cell-dependent response. induce immune-regulatory mechanisms, which limit efficacy IT. The co-administration anti-CD25 monoclonal antibody (mAb), targeting immune-suppressive CD4+CD25+FoxP3+ regulatory (Treg) cells, slightly augmented IL-21-based However, anti-CD4 mAb combined even higher cure rate (80%). potent synergistic effect achieved was related complete depletion Treg possibly other tumour-conditioned cell subsets. Mice receiving IL-21-releasing vaccine+anti-CD4 recovered their counts 90 days immunity NB. Preliminary data indicate administration recombinant (r) limited effects but co-treatment strongly These open new perspectives for use conjunction lymphodepletion