Figure 1.

Systemic delivery of donor bone marrow (BM) leukocytes ex vivo loaded with TNF-armed MYXV increases mean survival and reduces tumor burden in mice with K7M2-Luc lung metastatic osteosarcoma

(A) Diagram of experimental setup. K7M2-Luc cells implanted at day 0 via tail vein intravenous (i.v.) injection into BALB/c mice. Single dose treatment with test virus pre-loaded ex vivo on BALB/c BM leukocytes was at 3 days after tumor inoculation. Animals were then followed for 60 days. (B) Kaplan-Meier survival curves of animals treated with BM ex vivo loaded with either armed vMyx-hTNF (n = 8) (MYXV-TNF) or unarmed MYXV gene knockouts (vMyx-11KO [n = 8] or vMyx-135KO [n = 7]). Mice treated with vMyx-hTNF survived significantly longer than did animals treated with unarmed viruses or that were left untreated (n = 7). (C) Representative luminescence signals from K7M2-Luc-induced lung metastases at 2 weeks after tumor inoculation. Data shown (mean±SD) for unarmed BM+MYXV are for vMyx-135KO. (D) Representative luminescence images from K7M2-Luc-induced lung metastases at 2 weeks after tumor inoculation. (i) Control animals that received no treatment at 2 weeks after tumor inoculation. (ii) Animals that received BM ex vivo loaded with unarmed vMyx-135KO treatment (BM+MYXV) at 2 weeks after tumor inoculation. (iii) Animals that received BM ex vivo loaded with vMyx-hTNF (BM+MYXV-TNF) treatment at 2 weeks after tumor inoculation.