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. 2020 Mar 26;8(1):e000415. doi: 10.1136/jitc-2019-000415

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© Author(s) (or their employer(s)) 2020. 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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VVΔTKΔN1L-IL12 is an effective surgical adjuvant treatment in vivo. (A) Lewis lung carcinoma (LLC) tumors were established in the flanks of immune-competent C57/Bl6 mice (n=7/group). Once palpable, mice were injected intratumoral (i.t) with 1×10⁸ PFU VVΔTKΔN1L, VVΔTKΔN1L-mIL12 or PBS daily for 5 days (n=8–10/group). (A) Tumor growth was monitored until resection. A two-way analysis of variance (ANOVA) with post hoc Tukey tests was used to assess significance at each time point. (B) Overall survival was monitored using Kaplan-Meier survival analysis with log rank (Mantel-Cox) tests. (C) LLC tumors were treated as above. Tumors were surgically resected 7 days after the final dose of virus. Mice were sacrificed at day 15, H&E stained and analyzed for the presence of metastasis by a pathologist blinded to treatment groups. Lungs were scored as negative or positive and a Fishers exact test used to determine significance. (D) Mice treated in (C) were assessed for long-term survival after treatment and surgical excision of tumors using Kaplan-Meier survival analysis with log rank (Mantel-Cox) tests. (E) LY2 murine head and neck tumors were established in the flanks of immune-competent C57/Bl6 mice (n=10/group). Once palpable, mice were injected i.t with 1×10⁸ PFU VVΔTKΔN1L, VVΔTKΔN1L-mIL12 or PBS daily for 5 days. Tumor growth was monitored until resection 6 days following the last treatment. A two-way ANOVA with post hoc Tukey tests was used to assess significance at each time point. Significance at day 10 is shown. (F) LY2 tumors were treated as above and recurrence at the excision site or lymph node metastasis on sacrifice recorded. (G) LY2 tumors were treated as above and survival post resection monitored using Kaplan-Meier survival analysis with log rank (Mantel-Cox) tests. (H) Hamster HCPC1 tumors were established in the flank of Syrian hamsters. Once palpable, hamsters were injected i.t with 1×10⁸ PFU VVΔTKΔN1L, VVΔTKΔN1L-hIL12 or PBS daily for 5 days (n=10/group). The effect of treatment on the primary tumor is shown. Six days following the last treatment, remaining tumors were surgically excised (PBS n=9; VVΔTKΔN1L n=8; VVΔTKΔN1L-hIL12 n=5) and recurrence monitored. In all cases, the mean±SEM is shown. *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001.