Potentiation of the efficacy of murine L1210 leukemia vaccine by a novel immunostimulator 7-thia-8-oxoguanosine: increased survival after immunization with vaccine plus 7-thia-8-oxoguanosine.
We have investigated the ability of a novel immunopotentiator, 7-thia-8-oxoguanosine (7T8OG) to increase the efficacy of a weakly immunogenic murine L1210 leukemia vaccine. The vaccine was prepared by irradiating L1210 leukemia cells in a cesium source with a total of 6000-R dose. DBA/2 mice were treated with 150 mg/kg 7T8OG and/or with vaccine consisting of 10(7) irradiated cells. In combination therapy, mice first received the vaccine and then were injected with 75 mg/kg 7T8OG 2 h and 4 h after vaccination. One week after the last treatment all mice were inoculated with 10(4) live leukemia cells intraperitoneally. Control, untreated mice (n = 66) injected with 10(4) live leukemia cells had a mean survival time +/- standard error of 10.5 +/- 0.2 days. Treating mice (n = 66) with one, two or three doses of 7T8OG administered i.p. 1 week apart did not increase survival (mean survival time = 10.7 days). Mice immunized with one, two or three doses of vaccine had 14.5 +/- 1.1, 45.4 +/- 6.2 and 68.3 +/- 10.6 days mean survival, respectively. 7T8OG-stimulated vaccination increased the survival dramatically. The best survival was noted when the mice were treated with 2x (vaccine + 7T8OG). Immunization of mice (n = 30) with this treatment regimen increased the mean survival to 156 +/- 10.0 days. Over 90% of mice that were treated this way had a cumulative survival time greater than 160 days. In contrast, only 12% of the mice immunized twice with the leukemia vaccine alone survived over 160 days. These results suggest a rationale for the use of this immuno-potentiator with various vaccines for a more effective immunization.
Sharma
B S
BS
ICN Nucleic Acid Research Institute, Costa Mesa, CA 92625.
Balazs
L
L
Jin
A
A
Wang
J C
JC
Jolley
W B
WB
Robins
R K
RK
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division; D003131:Combined Modality Therapy; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007114:Immunization; D007939:Leukemia L1210 / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D014612:Vaccines; D006151:Guanosine; C061136:isatoribine