Article Figures & Data
Figures
- Fig. 1.
Phenotypic characterization of oncolytic HSVs in Neuro-2A cells. Neuro-2A cell monolayers were infected with the indicated viruses at 0.1 pfu/cell. Micrographs were taken at 24 h after infection (original magnification, ×200).
- Fig. 2.
Therapeutic effect of oncolytic HSVs against established neuroblastomas. Tumors were established on the right flank of immunocompetent A/J mice by s.c. implantation of 5 × 105 cells. Seven days later, viruses were injected into the tumor at a dose of 1 × 107 pfu. Tumor size was measured twice a week, and tumor volumes were determined as described in Materials and Methods.
, P < 0.05, FusOn-H2 versus PBS; , P < 0.05, FusOn-H2 versus aco-1; , P < 0.05, FusOn-H2 versus Synco-2D. - Fig. 3.
Tumor-specific CTL activity after virotherapy. Neuroblastoma was established as described in the legend to Fig. 2. Mice then received either one (A) or two (B) injections of virus. Mice were sacrificed 7 d after the last virus injection and the cytotoxic activity of effector cells prepared from spleens was measured against either Neuro-2A cells (A and B) or syngeneic Sa-I sarcoma cells (C). Effector cells from the same preparation used in (C) were also studied with the ELISPOT assay (see Materials and Methods) to determine the frequency of tumor-specific CTLs (D).
, P < 0.05, FusOn-H2 versus PBS; , P < 0.05, FusOn-H2 versus Baco-1; , P < 0.05, FusOn-H2 versus Synco-2D. - Fig. 4.
Comparison of Th1 cytokine secretion by CTLs from mice treated with different oncolytic HSVs. The CTLs were from the same pool used in Fig. 3B. Supernatants were collected from wells containing 5 × 104 splenocytes that had been stimulated with either irradiated Neuro-2A or Sa-I cells. The concentration of cytokines was measured with the BD Mouse Th1/Th2 Cytokine Cytometric Bead Array Kit according to the manufacturer's instructions.
- Fig. 5.
Growth of tumors implanted in the opposite flank of mice receiving virotherapy. Neuroblastoma was established in the right flank of A/J mice by s.c. injection of 5 × 105 Neuro-2A cells. Seven days later, the tumor nodules were injected with oncolytic virus, and new tumors (5 × 105 Neuro-2A cells) were established in the left flank. At 2 wk postimplantation, the resultant secondary tumor nodules were explanted and their gross appearance (A) and weight (B) were recorded. Statistical comparison of tumor weights is shown on the graph.
- Fig. 6.
Therapeutic effect of oncolytic HSVs against neuroblastoma in nude mice. Neuroblastoma was initially established on the right flank of Hsd nude mice. Subsequent virotherapy and Neuro-2A tumor cell rechallenge were done as described in the legend to Fig. 5. A, growth curve for primary tumors implanted on the right flank and subsequently injected with oncolytic HSVs. B, growth profiles for tumors that were implanted in the opposite flank and not treated with virus.
, P < 0.05, FusOn-H2 versus PBS; , P < 0.05, FusOn-H2 versus Baco-1. Tumor growth rates among the three groups in (B) did not differ significantly at any time points. - Fig. 7.
Antitumor effect of adoptively transferred splenocytes. Splenocytes from the experiment described in Fig. 3B were used. Initially, 5 × 105 Neuro-2A cells were implanted in the right flank of A/J mice. Three days later, 1 × 107 splenocytes in 100 μL of HBSS were adoptively transferred to the mice (n = 5 mice per group) by tail vein injection. Tumor size was measured once a week and tumor volume was determined as described in Materials and Methods.
, P < 0.05, FusOn-H2 versus PBS; , P < 0.05, FusOn-H2 versus Baco-1.
Volume 13, Issue 1
