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Effectiveness of slow-release systems in CD40 agonistic antibody immunotherapy of cancer

机译：缓释系统在CD40激动剂抗体免疫疗法中的有效性

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Slow-release delivery has great potential for specifically targeting immune-modulating agents into the tumor-draining area. In prior work we showed that local treatment of slowly delivered anti-CD40 antibody induced robust anti-tumor CD8+ T cell responses without systemic toxicity. We now report on the comparison of two slow-release delivery systems for their use in antibody-based immunotherapy of cancer. Anti-CD40 agonistic antibody delivered locally in mineral oil Montanide ISA 51 or in dextran-based microparticles activated tumor-specific T cell activation. Both slow-release formulations significantly decreased systemic side-effects compared to systemic administration of anti-CD40 antibody. However, dextran-based microparticles caused serious local inflammation associated with unwanted rapid outgrowth of tumors instead of the tumor clearance observed with delivery in Montanide. We therefore conclude that Montanide ISA 51 is to be preferred as a slow-release agent for CD40 agonist immunotherapy of cancer. (C) 2014 Elsevier Ltd. All rights reserved.
机译：缓释递送具有将免疫调节剂特异性靶向肿瘤引流区域的巨大潜力。在先前的工作中，我们显示了缓慢递送的抗CD40抗体的局部治疗诱导了强大的抗肿瘤CD8 + T细胞反应，而没有全身毒性。现在我们报告两种缓释递送系统在基于抗体的癌症免疫治疗中的比较。在矿物油Montanide ISA 51中或在基于葡聚糖的微粒中局部递送的抗CD40激动抗体激活了肿瘤特异性T细胞活化。与全身施用抗CD40抗体相比，两种缓释制剂均显着降低了全身副作用。然而，基于葡聚糖的微粒引起严重的局部发炎，这与不希望的肿瘤迅速长出有关，而不是在蒙太尼中观察到的肿瘤清除率高。因此，我们得出结论，Montanide ISA 51是首选的CD40激动剂免疫疗法用于癌症的缓释剂。 （C）2014 Elsevier Ltd.保留所有权利。

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