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IDT4 and its modified control, IDT4m7 (which removes
immunostimulation) were injected into mice that had previously
established HPV-driven tumours. The bi-functional IDT4 was more
potent at reducing tumour growth compared to IDT4m7 (Fig. 9.7a).
Interestingly, we noted that the use of a highly immunostimulatory,
but non-HPV targeting, siRNA was also able to exert anti-tumoural
effects at day 10 (Fig. 9.7b), but this effect was not apparent by day
14, suggesting bi-functional siRNA provides superior long-term anti-
tumour control (Fig. 9.7b).
(a)
(b)
siRNA
siRNA
Figure 9.7
Treatments of established tumours with siRNAs show
a reduction in tumour growth. TC-1 cells (1 × 10
6
cells)
were subcutaneously injected into C57BL/6 mice on day 0
before mice were treated intravenously with 40 µg siRNAs
encapsulated in liposomes on days 5, 8, and 12. (a) Tumour
growth reduction by RNAi is independent of TLR7 activation.
Treatments carried out with IDT-4 as an immunostimulatory
D-siRNA and IDT-4m7 as a non-immunostimulatory D-siRNA,
both with RNAi ability for HPV16 E6/E7. Caliper measure-
ments of tumours were carried out on day 14 post initial
subcutaneous injections. Error bar represents ±SEM with
= 6.
Significant differences between control and IDT-4 and control and
IDT-4m7 are indicated (*
n
< 0.01; two-sided t-test).
(b) Activation of TLR7 independent of RNAi results in a transient
anti-tumour effect. Treatments carried out with 40 µg siRNA
mouse per intravenous (i.v.) injection as previously described
with BP1 Mod2 (highly immunostimulatory for IFNa) and bgal
924 (non-immunostimulatory for IFNa), both not targeting
HPV16 E6/E7. Caliper measurements of tumours were carried
out on day 10 post initial subcutaneous injections. Significant
difference between control and BP1 Mod2 is indicated (***
P
< 0.05, **
P
P
<
0.001; two-sided t-test). Error bars represents ±SEM with
n
= 5.
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