4.7 Article

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

Journal

CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 12, Pages 3541-3555

Publisher

SPRINGER
DOI: 10.1007/s00262-021-02946-z

Keywords

Melanoma; Oncolytic virus; PD-1 blockade; Combination therapy; Tumor immune infiltration; Tumor immune recognition

Funding

  1. National Natural Science Foundation of China [81372453, 81572999, 31701220]
  2. Sichuan Science and Technology Project [2013ZZ0004]
  3. Shanghai Institutes for Biological Science, Chinese Academy of Sciences
  4. Sichuan Huiyang Life Science and Technology Corp. Research Program [Y363S21763]
  5. Conba Group
  6. Zhejiang Sci-Tech University

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The combination therapy of localized ZD55-IL-24 and systemic PD-1 blockade shows a synergistic inhibition of both local and distant established tumors in an immunocompetent mouse model. This synergistic therapeutic effect is associated with the promotion of tumor immune infiltration and recognition, primarily facilitated by ZD55-IL-24 therapy. The study suggests a rationale for further investigation of this combination therapy in clinical settings.
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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