Figure 4

Nk4 therapy of LLC tumours. (a) Pattern of AAV-mediated gene expression in muscle tissue. In vivo luciferase expression from AAV2-Luc transduced muscle tissue was assessed using live whole body imaging (IVIS) at various time-points post delivery. Mean luminescence (p/sec/cm^2/sr) per gene copy ± S.E is shown. (b) Assessment of AAV-mediated in vivo delivery and expression of Nk4. Quadriceps tissue from animals administered AAV2-Nk4 was excised at day 3 and DNA and RNA extracted. Nk4 DNA and mRNA was readily detected by PCR in treated muscle tissue confirming AAV mediated delivery and transcription of Nk4. No Nk4 DNA or mRNA was detected in untreated controls. (c-d) Effect of systemic production of NK4 on SC LLC volume. Animals were IM administered AAV-Nk4 or AAV2-BB (control) or no particles (PBS) 14 days prior to inoculation with LLC tumours. (c) Although tumour growth in the AAV2-Nk4 group was reduced when compared with the AAV2-BB injected control group and the untreated group at day 27, it proved to be statistically insignificant. (d) Although animal survival in the AAV2-NK4 group was increased when compared with the AAV2-BB injected control group and the untreated group, it proved to be statistically insignificant (p = 0.26, p = 0.06 respectively). (e) Effect of combined immune gene and Nk4 therapies on LLC tumours. Animals were IM administered AAV2-Nk4 or AAV2-BB (control) or no particles (PBS) 14 days prior to induction of SC LLC tumours. Established LLC tumours were then IT administered AAV2-GB, AAV2-BB (control) or no particles (PBS) and growth monitored. Although tumour growth in the combined AAV2-Nk4/AAV2-GB was reduced when compared with the AAV2-BB control group and the untreated group, it proved to be statistically insignificant (p = 0.37, p = 0.51 respectively). (* Statistical significance (p < 0.05))