Group |
No. Mice |
Test Material |
Dose |
ROA |
Frequency |
1 |
10 |
Vehicle, LNP |
27 ul |
intratumor |
3 treatments/wk for |
2 |
10 |
LNP + mutant plasmid cDNA A1 AR |
50 µg |
intratumor |
3 treatments/wk for |
3 |
10 |
LNP + mutant plasmid cDNA A1 AR |
100 µg |
intratumor |
3 treatments/wk for |
4 |
10 |
LNP + mutant plasmid cDNA A1 AR |
200 µg |
intratumor |
3 treatments/wk for |
5 |
10 |
LNP + wild type plasmid cDNA A1 AR |
150 µg |
intratumor |
3 treatments/wk for |
6 |
10 |
LNP + INFγ |
27 ul |
intratumor |
3 treatments/wk for |
7 |
10 |
Paclitaxel |
15 mg/kg |
IV* |
Twice/week for 6 weeks |
Table 1 : Treatment Schedule
|
Therapy Days, Treatment Period |
Therapy Days, Recovery Period |
|||||||
Group |
Statistic |
-8 |
0 |
20 |
27 |
39 |
41 |
46 |
53 |
Grp1 |
Mean |
0 |
118.2 |
496.4 |
926.7 |
1249.5 |
1234.5 |
1375.4 |
1719.3 |
SEM |
0 |
5 |
77 |
122 |
218 |
251 |
218 |
161 |
|
Grp2 |
Mean |
0 |
117.3 |
407.2 |
657.5 |
816.8 |
677.1 |
834.4 |
829.5 |
SEM |
0 |
7 |
80 |
150 |
269 |
209 |
221 |
186 |
|
p vs Grp1 |
1 |
0.924 |
0.435 |
0.184 |
0.232 |
0.141 |
0.153 |
0.022 |
|
Grp3 |
Mean |
0 |
119.5 |
316.5 |
565.8 |
659.8 |
500 |
478.1 |
397.2 |
SEM |
0 |
6 |
105 |
179 |
254 |
199 |
187 |
134 |
|
p vs Grp1 |
1 |
0.868 |
0.185 |
0.116 |
0.098 |
0.056 |
0.023 |
0.002 |
|
Grp4 |
Mean |
0 |
114.5 |
178.9 |
376.4 |
167.5 |
147.1 |
107.1 |
124.1 |
SEM |
0 |
6 |
93 |
187 |
84 |
72 |
53 |
64 |
|
p vs Grp1 |
1 |
0.664 |
0.02 |
0.03 |
0.002 |
0.009 |
0.007 |
0.003 |
|
Grp5 |
Mean |
0 |
119.6 |
275.3 |
472.5 |
568.8 |
622.9 |
724.8 |
903.8 |
SEM |
0 |
5 |
79 |
134 |
168 |
188 |
232 |
290 |
|
p vs Grp1 |
1 |
0.843 |
0.062 |
0.023 |
0.029 |
0.094 |
0.089 |
0.052 |
|
Grp6 |
Mean |
0 |
119.2 |
335.8 |
610 |
667.3 |
753.1 |
749.4 |
1175.5 |
SEM |
0 |
5 |
62 |
129 |
162 |
206 |
180 |
271 |
|
p vs Grp1 |
1 |
0.883 |
0.125 |
0.094 |
0.057 |
0.193 |
0.089 |
0.173 |
|
Grp7 |
Mean |
0 |
119.3 |
14.8 |
0 |
0 |
0 |
0 |
0 |
SEM |
0 |
5 |
6 |
0 |
0 |
0 |
0 |
0 |
|
p vs Grp1 |
1 |
0.874 |
0 |
0 |
0.001 |
0.006 |
0.006 |
0.004 |
|
Significance (p) was calculated by Student’s t-test. P value < 0.05 was considered statistically significant. Grp denotes Group
Table 2 : Effect of Treatment on Average Tumor Volume (mm3) Versus Group 1
Therapy days ( Treatment Period) |
Recovery Period |
||||||||
Group |
Statistic |
-8 |
0 |
20 |
27 |
39 |
41 |
46 |
53 |
Grp1 |
Mean |
0.0 |
118.2 |
496.4 |
926.7 |
1249.5 |
1234.5 |
1375.4 |
1719.3 |
|
SEM |
0 |
5 |
77 |
122 |
218 |
251 |
218 |
161 |
Grp2 |
Mean |
0.0 |
117.3 |
407.2 |
657.5 |
816.8 |
677.1 |
834.4 |
829.5 |
|
SEM |
0 |
7 |
80 |
150 |
269 |
209 |
221 |
186 |
|
% vs Grp 1 |
|
1% |
18% |
29% |
35% |
45% |
39% |
52% |
Grp3 |
Mean |
0.0 |
119.5 |
316.5 |
565.8 |
659.8 |
500.0 |
478.1 |
397.2 |
|
SEM |
0 |
6 |
105 |
179 |
254 |
199 |
187 |
134 |
|
% vs Grp 1 |
|
-1% |
36% |
39% |
47% |
59% |
65% |
77% |
Grp4 |
Mean |
0.0 |
114.5 |
178.9 |
376.4 |
167.5 |
147.1 |
107.1 |
124.1 |
|
SEM |
0 |
6 |
93 |
187 |
84 |
72 |
53 |
64 |
|
% vs Grp 1 |
|
3% |
64% |
59% |
87% |
88% |
92% |
93% |
Grp5 |
Mean |
0.0 |
119.6 |
275.3 |
472.5 |
568.8 |
622.9 |
724.8 |
903.8 |
|
SEM |
0 |
5 |
79 |
134 |
168 |
188 |
232 |
290 |
|
% vs Grp 1 |
|
-1% |
45% |
49% |
54% |
50% |
47% |
47% |
Grp6 |
Mean |
0.0 |
119.2 |
335.8 |
610.0 |
667.3 |
753.1 |
749.4 |
1175.5 |
|
SEM |
0 |
5 |
62 |
129 |
162 |
206 |
180 |
271 |
|
% vs Grp 1 |
|
-1% |
32% |
34% |
47% |
39% |
46% |
32% |
Grp7 |
Mean |
0.0 |
119.3 |
14.8 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
|
SEM |
0 |
5 |
6 |
0 |
0 |
0 |
0 |
0 |
|
% vs Grp 1 |
|
-1% |
97% |
100% |
100% |
100% |
100% |
100% |
Grp denotes Group
Table 3 : Effect of Test Compounds on Tumor Reduction (%) Versus Group 1
|
Therapy days ( treatment period) |
Recovery Period |
|
||||||
Group |
Statistic |
-8 |
0 |
20 |
27 |
39 |
41 |
46 |
53 |
Grp1 |
Mean |
0.0 |
118.2 |
496.4 |
926.7 |
1249.5 |
1234.5 |
1375.4 |
1719.3 |
SEM |
0 |
5 |
77 |
122 |
218 |
251 |
218 |
161 |
|
p vs Grp5 |
1.000 |
0.843 |
0.062 |
0.023 |
0.029 |
0.094 |
0.089 |
0.052 |
|
Grp2 |
Mean |
0.0 |
117.3 |
407.2 |
657.5 |
816.8 |
677.1 |
834.4 |
829.5 |
SEM |
0 |
7 |
80 |
150 |
269 |
209 |
221 |
186 |
|
p vs Grp5 |
1.000 |
0.799 |
0.259 |
0.370 |
0.448 |
0.855 |
0.744 |
0.848 |
|
Grp3 |
Mean |
0.0 |
119.5 |
316.5 |
565.8 |
659.8 |
500.0 |
478.1 |
397.2 |
SEM |
0 |
6 |
105 |
179 |
254 |
199 |
187 |
134 |
|
p vs Grp5 |
1.000 |
0.989 |
0.757 |
0.681 |
0.769 |
0.668 |
0.429 |
0.164 |
|
Grp4 |
Mean |
0.0 |
114.5 |
178.9 |
376.4 |
167.5 |
147.1 |
107.1 |
124.1 |
SEM |
0 |
6 |
93 |
187 |
84 |
72 |
53 |
64 |
|
p vs Grp5 |
1.000 |
0.540 |
0.444 |
0.682 |
0.052 |
0.036 |
0.027 |
0.035 |
|
Grp5 |
Mean |
0.0 |
119.6 |
275.3 |
472.5 |
568.8 |
622.9 |
724.8 |
903.8 |
SEM |
0 |
5 |
79 |
134 |
168 |
188 |
232 |
290 |
|
Grp6 |
Mean |
0.0 |
119.2 |
335.8 |
610.0 |
667.3 |
753.1 |
749.4 |
1175.5 |
SEM |
0 |
5 |
62 |
129 |
162 |
206 |
180 |
271 |
|
p vs Grp5 |
1.000 |
0.953 |
0.556 |
0.469 |
0.686 |
0.656 |
0.937 |
0.538 |
|
Grp7 |
Mean |
0.0 |
119.3 |
14.8 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
SEM |
0 |
5 |
6 |
0 |
0 |
0 |
0 |
0 |
|
p vs Grp5 |
1.000 |
0.962 |
0.009 |
0.000 |
0.001 |
0.009 |
0.012 |
0.018 |
|
Significance (p) was calculated by Student’s t-test. P value < 0.05 was considered statistically significant. Grp denotes Group
Table 4 : Effect of Treatment on Average Tumor Volume (mm3) Versus Group 5
|
Therapy days ( Treatment Period) |
Recovery Period |
|||||||
Group |
Statistic |
-8 |
0 |
20 |
27 |
39 |
41 |
46 |
53 |
Grp1 |
Mean |
0.0 |
118.2 |
496.4 |
926.7 |
1249.5 |
1234.5 |
1375.4 |
1719.3 |
SEM |
0 |
5 |
77 |
122 |
218 |
251 |
218 |
161 |
|
% vs Grp 5 |
|
1% |
-80% |
-96% |
-120% |
-98% |
-90% |
-90% |
|
Grp2 |
Mean |
0.0 |
117.3 |
407.2 |
657.5 |
816.8 |
677.1 |
834.4 |
829.5 |
SEM |
0 |
7 |
80 |
150 |
269 |
209 |
221 |
186 |
|
% vs Grp 5 |
|
2% |
-48% |
-39% |
-44% |
-9% |
-15% |
8% |
|
Grp3 |
Mean |
0.0 |
119.5 |
316.5 |
565.8 |
659.8 |
500.0 |
478.1 |
397.2 |
SEM |
0 |
6 |
105 |
179 |
254 |
199 |
187 |
134 |
|
% vs Grp 5 |
|
0% |
-15% |
-20% |
-16% |
20% |
34% |
56% |
|
Grp4 |
Mean |
0.0 |
114.5 |
178.9 |
376.4 |
167.5 |
147.1 |
107.1 |
124.1 |
SEM |
0 |
6 |
93 |
187 |
84 |
72 |
53 |
64 |
|
% vs Grp 5 |
|
4% |
35% |
20% |
71% |
76% |
85% |
86% |
|
Grp5 |
Mean |
0.0 |
119.6 |
275.3 |
472.5 |
568.8 |
622.9 |
724.8 |
903.8 |
SEM |
0 |
5 |
79 |
134 |
168 |
188 |
232 |
290 |
|
Grp6 |
Mean |
0.0 |
119.2 |
335.8 |
610.0 |
667.3 |
753.1 |
749.4 |
1175.5 |
SEM |
0 |
5 |
62 |
129 |
162 |
206 |
180 |
271 |
|
% vs Grp 5 |
|
0% |
-22% |
-29% |
-17% |
-21% |
-3% |
-30% |
|
Grp7 |
Mean |
0.0 |
119.3 |
14.8 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
SEM |
0 |
5 |
6 |
0 |
0 |
0 |
0 |
0 |
|
% vs Grp 5 |
|
0% |
95% |
100% |
100% |
100% |
100% |
100% |
|
Grp denotes Group
Table 5 : Effect of Test Compounds on Tumor Reduction (%) Versus Group 5
Figure1: Effect of test materials on tumor growth (mm3) was measured in a xenograph model of human PC-3 prostate cancer in athymic nude mice during a 6-week treatment period and a 2-week follow-up period Effect of Test Materials on Tumor Growth
Figure2: Tumor reduction (% change) in the treatment groups 2 - 7 versus group 1 (diluent control) was measured in a xenograph model of human PC-3 prostate cancer in athymic nude mice during a 6-week treatment period and a 2-week recovery period. Grp denotes Group Tumor Reduction (%) Versus Group 1
Figure3: Plasmid Map
Tables at a glance
Figures at a glance