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. 2017 Oct 25;7:14049. doi: 10.1038/s41598-017-14417-6

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Delayed combination therapy with anti-PD-1 and anti-CD4 mAb is effective and leads to a long-lasting immunity to NB. (a) The combined treatment with anti-PD-1 and anti-CD4 mAb potently inhibits Neuroblastoma progression even if started at a later time point (+6 days from challenge). P values of delayed combined treatments vs irrelevant Ab controls are indicated (Wilcoxon log-rank test). Percentages of progression-free mice are indicated on the Y-axis and the fraction of progression-free mice of each group is given in brackets. (b) IVIS analysis representation of Neuro2a-luc NB development in mice receiving delayed combined treatments at the indicated time-points from challenge. (c) All mice cured by combined anti-PD-1/anti-CD4 mAb therapy were resistant to a subsequent i.v. challenge (at 90 days from primary challenge) with a fully tumorigenic dose of Neuro2a-luc cells. P values of delayed combined treatments vs irrelevant Ab controls are indicated (Wilcoxon log-rank test).