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.
Highlights
Melanoma, the most aggressive type of skin cancer, has a poor prognosis, with a median overall survival of 8–10 months and a 5-year survival rate of 20% [1]
We further investigated whether ZD55-IL-24 therapy in combination with PD-1 immune checkpoint inhibition could facilitate primary tumor as well as metastatic lesions rejection in B16-bearing immunocompetent mouse model
Among the above immune cells, the antitumor effect of neutrophils, natural killer T (NKT) cells, M1 macrophages, CD8+ T cells and CD4+ T cells has been well-documented [5, 23,24,25,26,27]. These results indicated that ZD55-IL-24 was able to help PD-1 blockade to overcome the weakness of relatively low tumor immune infiltration in primary tumors
Summary
The most aggressive type of skin cancer, has a poor prognosis, with a median overall survival of 8–10 months and a 5-year survival rate of 20% [1]. Melanoma still exhibits a poor prognosis because of its rapid proliferation, and therapy remains challenging for physicians [2]. In the past several years, five breakthrough anti-melanoma agents have been approved by the US Food and Drug Administration (FDA). These agents include small-molecule inhibitors of BRAF and MEK, immunotherapeutic antibodies directed at cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), and the modified oncolytic herpes virus T-VEC [3]. The current treatments for melanoma have been successful, to cure or make
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