Oncolytic adenovirus H101 ameliorate the efficacy of anti-PD-1 monotherapy in colorectal cancer

Background: Immune checkpoint blockade therapy with anti-programmed cell death (PD)-1 antibodies provides therapeutic effect for many patients of various cancers but remains inadequate in colorectal cancer (CRC) patients. The present study aims to assess the efficacy of oncolytic adenovirus (Onco^Ad ) in enhancing the anti-PD-1 treatment of CRC.

Methods: The estimating relative subsets of RNA transcripts algorithm was used for estimating the infiltrated immune cells in melanoma and CRC tissues. The efficacy of Onco^Ad with anti-PD-1 monotherapy was performed in a CT26 CRC mouse model in vivo. Flow cytometric analysis of peripheral blood and tumor tissues determined the difference anti-tumor immune efficacy of Onco^Ad with anti-PD-1 monotherapy.

Results: The Cancer Genome Atlas database indicated that CD8⁺ T cells and regulatory T cells were significantly elevated in melanoma compared to CRC cohorts. Moreover, intratumor injection of oncolytic adenovirus enhanced T cell infiltration and decreased Treg percentages in the CT26 CRC colorectal cancer mouse model. Combinatorial Onco^Ad with anti-PD-1 antibody treatment markedly enhanced the anti-tumor efficacy of anti-PD-1 by significantly decreasing the tumor volume and reducing tumor growth in a CRC mouse model. To the end, Onco^Ad treatment increased the CD8/Treg ratio, indicating that Onco^Ad intratumor injection ameliorate the anti-tumor immune response of anti-PD-1 therapy.

Conclusion: The present study elucidates that Onco^Ad promotes intratumor T cell infiltration and improves anti-PD-1 immunotherapy, thereby providing a potent combinatorial therapeutic strategy for CRC.