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. 2022 Jun 10;10(6):e004762. doi: 10.1136/jitc-2022-004762

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© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.

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Therapeutic delivery of PD-1 inhibitors by YST-OVH potentiates the antitumor efficacy of immune checkpoint blockade. (A) Treatment scheme for bilateral flank Hepa1-6 tumor-bearing PD-1-HU mice. Mice bearing tumors received monotherapy or combination therapy with YST-OVH and anti-CTLA-4. Tumor growth of injected tumors (B) and distant tumors (C). (D) Individual tumor growth curves of injected tumors. (E) Individual tumor growth curves of distant tumors. (F) Treatment scheme for a syngeneic Hepa1-6 tumor model. Mice-bearing tumors received monotherapy or combination therapy with YST-OVH and anti-TIM-3. Tumor growth was monitored over a 27-day period. (G) Treatment scheme for a syngeneic Hepa1-6 tumor model. Mice-bearing tumors received monotherapy or combination therapy with OVs and anti-CTLA-4, and tumors were collected on day 9 post-treatment and subjected to RNA-seq analysis. (H) GO enrichment analysis showing the top 10 most enriched pathways. (I) Heatmap showing the expression of differentially expressed antigen processing and presentation genes. (J) Heatmap showing the expression of differentially expressed T cell activation genes. Gene expression was normalized to values obtained for an untreated control. Data represent results from one of three (A) or one of two (F) independent experiments with n=9 to n=10 per group. All values are presented as the mean±SEM; repeated-measure ANOVA (B, C, F). CR, complete response; OVs, oncolytic viruses; PR, partial response. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001. YST-OVH, oncolytic herpes simplex virus-1 expressing PD-1 inhibitors; ANOVA, analysis of variance; PFU, plaque-forming units.