Summary
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 107 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 104 live leukemia cells intraperitoneally. Control, untreated mice (n = 66) injected with 104 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 2× (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.
Similar content being viewed by others
References
Arlinhaus RB (1989) Vaccines against tumor antigens. Adv Vet Sci Comp Med 288: 309
Berzofsky JA (1988) Immunodominance in T lymphocyte recognition. Immunol Lett 18: 83
Bystryin JC, Jacobsen S, Harris M, Roses D, Sprayer J, Levin M (1986) Preparation and characterization of a polyvalent human melanoma antigen vaccine. J Biol Response Mod 5: 211
Cantrell JL, Finn DJ (1987) Role of novel adjuvants in specific active immunotherapy. In: Mitchell MS (ed) Progress in clinical and biological research; immunity to cancer: II. Liss, New York, p 297
Cox DR, Oakes D (1984) Analysis of survival data. Chapman and Hill, London, p 1
Dixon WJ (1985) BMDP statistical software. University of California Press, Berkley
Djeu JY, Heinbaugh JA, Holden HJ, Herberman RB (1979) Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol 122: 175
Earl PL, Moss B, Morrison RP, Wehrly K, Nishio J, Chesebro B (1986) T lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirusenv gene recombinant. Science 234: 728
Gidlund MA, Orn A, Wigzell H, Senik A, Gresser I (1978) Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature 273: 759
Hanna MG, Peters LC (1978) Immunotherapy of established micrometastases with bacillus Calmette-Guerin tumor cell vaccine. Cancer Res 38: 204
Hoover HC, Surdyka MS, Dangel RB, Peter LC, Hanna MG (1985) Prospectively randomized trial of adjuvant active-specific immunotherapy for human colorectal cancer. Cancer 55: 1236
Kalbfeisch JD, Prentice RL (1980) The statistical analysis of failure time data. Wiley, New York, p 1
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Statist Assoc 58: 457
Lee V, Sharma B, Jolley WB (1989) 7-Thia-oxoguanosine induces de novo expression of surface Ia antigens and Ig. FASEB J 3: 794
Livingston PO (1987) Experimental and clinical studies with active specific immunotherapy. In: Mitchell MS (ed) Progress in clinical and biological research; immunity to cancer: II. Liss, New York, p 309
Mitchell MS (1987) Active specific immunotherapy in the treatment of human cancers. In: Mitchell MS (ed) Progress in clinical and biological research: immunity to cancer: II. Liss, New York, p 323
Nagahara, Anderson J, Kini G, Dalley K, Larson S, Smee D, Sharama B, Jolley WB, Robins RK, Cottam B (1990) Thiazolo [4-5-d]-pyrimidine nucleosides. The synthesis of certain 3-β-d-ribo-furanosylthiazolo [4,5-d] pyrimidines as potential immunotherapeutic agents. Med Chem 33: 407
Neidhart JA, Murphy SC, Hennick LA, Wise HA (1980) Active Specific immunotherapy of stage IV veral carcinoma with aggregated tumor antigen adjuvant. Cancer 46: 1128
Prehn RT (1973) The immune reaction as a stimulator of tumor growth. Science 176: 70
Rosa FM, Cochet MM, Fellus M (1986) Interferon and major histocompatibility complex genes: a model to analyze eucaryotic gene regulation. Interferon 7: 47
Sahasrabudhe DM, Dekernion JB, Pontes JE, McCune CS, Ryan DM, O'Donnel RW (1986) Specific immunotherapy with suppressor functional inhibition for metastatic renal cell carcinoma. J Biol Response Mod 5: 581
Schiel HJ, Kyewski B, Oegen P, Schirrmacher V (1987) CD4+ helper T cells are required for resistance to highly metastatic murine tumor. Eur J Immunol 17: 1863
Sharma B, Odom LF (1979) Generation o killer lymphocytes in vitro against autologous leukemia cells with leukemic blast and BCG extract. Cancer Immunol Immunother 7: 99
Sharma B, Kohaio O, Mickey MR, Terasaki PI (1975) Effect of water soluble adjuvany on in vitro lymphocyte immunization. Cancer Res 35: 666
Sharma B, Jolley WB, Popow J, Robins RK, Cottam H (1988) N10 146, a novel nucleoside induces B cell proliferation, polyclonal antibody synthesis and enhances antigen specific primary antibody response. In: Proc. 3d Annual Conference on Clinical Immunology, San Francisco, p 27
Sharma B, Jin A, Balazs L, Mhaskar S, Jolley WB (1989) Inhibition of metastatic growth of murine melanoma tumor cells in lungs by 7-thia-8-oxoguanosine. FASEB J 3: 831
Smee DF, Alaghamandan HA, Cottam HB, Sharama B, Jolley WB, Robins K (1989) Broad-spectrum in vivo antiviral activity of 7-thia-8-oxoguanosine, a novel immunopotentiating agent. antimicrob Agents Chemother 33: 1487
Smee DF, Alaghamanadan HA, Jin A, Sharma B, Jolley WB (1990) roles of interferon and natural killer cells in the antiviral activity of 7-thia-8-oxoguanosine against Semiliki forest virus in mice. Antiviral Res 13: 91
Vanky F, Stuber G, Willems J, Sjowall K Larsson, Book K, Invert T, Peterffy A, Klein E (1988) Importance of MHC antigen expression on solid tumors in the interaction with autologous blood lymphocytes. Cancer Immunol Immunother 27: 213
Vanky F, Stuber G, Rosteim S, Klein E (1989) Auto tumor recognition following in vitro induction of MHC antigen expression on solid human tumors: stimulation of lymphocytes and generation of cytotoxicity-negative tumor cells. Cancer Immunol Immunother 28: 17
Wu J, Fitzgerald J, Sonis S, Ravikumar T, Wilson R (1987) Increased efficacy of immunotherapy using irradiated tumor cells. Cancer Immunol Immunother 24: 68
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sharma, B.S., Balazs, L., Jin, A. et al. 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. Cancer Immunol Immunother 33, 109–114 (1991). https://doi.org/10.1007/BF01742538
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01742538