Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model

在携带B16肿瘤的免疫功能正常小鼠模型中,通过联合使用武装溶瘤腺病毒ZD55-IL-24和免疫检查点阻断剂,可增强抗黑色素瘤疗效。

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作者:Hai-Jun Hu # ,Xiu Liang # ,Hai-Lang Li ,Huai-Yuan Wang ,Jin-Fa Gu ,Lan-Ying Sun ,Jing Xiao ,Jin-Qing Hu ,Ai-Min Ni ,Xin-Yuan Liu

Abstract

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.

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