ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.

中文翻译：

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武装溶瘤腺病毒 ZD55-IL-24 在免疫功能低下和免疫功能正常的小鼠模型中的给药策略优化

ZD55-IL-24 是一种武装溶瘤腺病毒，类似于但优于 ONYX-015。使用 ZD55-IL-24 的病毒治疗策略已被证明对几种癌症类型有效。然而，尚不清楚传统的给药策略是否能够发挥 ZD55-IL-24 的最大抗肿瘤功效。在这项研究中，我们试图优化 ZD55-IL-24 在 A375 免疫功能低下小鼠模型和 B16 免疫功能小鼠模型中的给药策略。尽管潜在的抗肿瘤机制完全不同，但在这两种小鼠肿瘤模型中获得的结果是相似的。我们发现 ZD55-IL-24 的抗肿瘤功效随着这两种模型中注射时间的增加而增加。然而，随着每次注射剂量的增加，没有观察到疗效的明显增加。我们的进一步研究表明，与传统的短期 ZD55-IL-24 治疗的给药策略相比，持续 ZD55-IL-24 治疗的给药策略可以达到更好的治疗效果。此外，无需每天注射；每 2 或 3 天注射一次，可达到同等疗效。最后，我们发现持续而非传统的短期 ZD55-IL-24 疗法可以与抗 PD-1 疗法协同作用以排斥 B16 免疫功能小鼠模型中的肿瘤。这些发现表明，ZD55-IL-24过去的给药策略实际上并不理想，通过优化给药策略可以进一步提高抗肿瘤功效。这项研究可能会为 ZD55-IL-24 治疗的临床适用给药方案的开发提供一些启示。