The antitumor effects of adenoviral-mediated, intratumoral delivery of interleukin 23 require endogenous IL-12.
The antitumor effects of adenoviral-mediated, intratumoral delivery of interleukin 23 require endogenous IL-12.
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DOI：
10.1038/cgt.2011.78
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发表时间：
2012-02
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
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IL-23是IL-12异二聚体细胞因子家族的成员，由p19和p40亚基组成，具有与IL-12相似的免疫刺激特性。我们以前已经证明，腺病毒介导的肿瘤内递送IL-23(Ad.IL-23)能够诱导全身抗肿瘤免疫。在这里，我们证明了腺病毒介导的肿瘤内注射后，Ad.IL-23需要内源性IL-12来发挥抗肿瘤作用。相反，Ad.IL-12不需要IL-23来发挥其抗肿瘤作用，尽管内源性IL-23似乎在IL-12诱导全身抗肿瘤免疫中起着重要作用。然而，尽管需要内源性IL-12，但IL-23和IL-12的联合传递甚至不能提供局部或全身的附加抗肿瘤效应，无论剂量如何。我们进一步证明，尽管单链IL-23(SLEL-23)的使用导致了更高的表达水平和更明显的IL-23介导的抗肿瘤作用，但与IL-12仍然没有协同作用。这些结果表明，虽然单独通过瘤内注射表达SLE-23或IL-12的腺病毒可以达到显著的抗肿瘤效果，并且IL-23需要内源性IL-12才能获得最大的抗肿瘤益处，但这些细胞因子的联合使用没有提供相加或协同作用。
IL-23 is a member of the IL-12 family of heterodimeric cytokines, comprised of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. We have demonstrated previously that adenoviral-mediated, intra-tumoral delivery of IL-23 (Ad.IL-23) was able to induce systemic anti-tumor immunity. Here we demonstrate that Ad.IL-23 requires endogenous IL-12 for conferring an anti-tumor effect after adenoviral-mediated intra-tumoral delivery. In contrast, Ad.IL-12 does not require IL-23 for its anti-tumor effects although endogenous IL-23 appears important for induction of systemic anti-tumor immunity by IL-12. However, despite the requirement for endogenous IL-12, co-delivery of IL-23 and IL-12 does not provide even an additive local or systemic anti-tumor effect, regardless of the dose. We further demonstrate that although the use of a single chain IL-23 (scIL-23) results in higher level of expression and a more pronounced IL-23-mediated anti-tumor effect, there is still no synergy with IL-12. These results demonstrate that whereas significant anti-tumor effects are achieved by intratumoral injection of adenovirus expressing either scIL-23 or IL-12 alone and that IL-23 requires endogenous IL-12 for maximum anti-tumor benefit, the combined use of these cytokines provides no additive or synergistic effect.
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