State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Cancer Immunol Immunother. 2021 Dec;70(12):3541-3555. doi: 10.1007/s00262-021-02946-z. Epub 2021 Apr 26.
Although the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model. Our further mechanism investigation reveals that synergistic therapeutic effect is associated with marked promotion of tumor immune infiltration and recognition in both local and distant tumors as well as spleens. PD-1 blockade has no obvious effect on promotion of tumor immune infiltration and recognition. Localized therapy with ZD55-IL-24, however, can help PD-1 blockade to overcome the limitation of relatively low tumor immune infiltration and recognition. This study provides a rationale for investigation of such combination therapy in the clinic.
尽管最近通过使用抗 PD-1 免疫疗法治疗黑色素瘤取得了成功，但这种方法的疗效仍有待提高。在这里，我们探索了武装溶瘤腺病毒 ZD55-IL-24 与 PD-1 阻断联合策略的可行性。我们发现，局部 ZD55-IL-24 与全身 PD-1 阻断联合治疗可协同抑制 B16 荷瘤免疫功能正常小鼠模型中局部和远处已建立的肿瘤。我们进一步的机制研究表明，协同治疗效果与局部和远处肿瘤以及脾脏中肿瘤免疫浸润和识别的显著促进有关。PD-1 阻断对促进肿瘤免疫浸润和识别没有明显作用。然而，局部 ZD55-IL-24 治疗可以帮助 PD-1 阻断克服肿瘤免疫浸润和识别相对较低的局限性。这项研究为在临床上研究这种联合治疗提供了依据。
