Abstract
The endogenous protein survivin is present in tumor cells and inhibits apoptosis. The influence of vaccination of mice by survivin fragments on growth of various types of tumors was studied in order to examine the possibility of creation of an antitumor vaccinating agent on its basis. Two peptides corresponding to the 118–144 and (80–88)-(153–165) sequences of survivin 2B were chosen and synthesized on the basis of literature data and theoretical calculations. Their ability to stimulate antibody production in mice of the C57BL/6J line (b-haplotype) and in BDF1 hybrids (b × d-haplotype) was investigated. Both peptides were shown to stimulate production of antibodies that bound the recombinant survivin in the BDF1 mice. Immunization of BDF1 and C57BL/6J mice with the recombinant survivin resulted in formation of antibodies that reacted with 118–144 peptide. The effect of preventive vaccination with the peptides and the recombinant protein on dynamics of growth of several species of tumors was studied. Vaccination with the (80–88)-(153–165) peptide was found to cause an antitumor effect in BDF1 mice suffered from sarcoma S-37. Thus, creation of antitumor agent on the basis of this peptide is a promising area of further studies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- IFA:
-
incomplete Freund’s adjuvant
- CFA:
-
complete Freund’s adjuvant
- DIEA:
-
N-ethyldiisopropylamine
- DIPC:
-
N,N′-diisopropylcarodiimide
- DMAP:
-
4-dimethylaminopyridine
- Fmoc:
-
9-fluorenylmethoxycarbonyl
- MHC:
-
major histocompatibility complex
- Pbf:
-
2,2,4,6,7-pentamethyldihydrobenzofurane-5-sulfonyl
- RecSur:
-
recombinant survivin
- TIS:
-
triisopropyl silane
- TBTU:
-
tetrafluoroborate-O-(benzotriazole-1-yl)-N,N,N′,N′-tetramethylurea
References
Altieri, D.C. and Marchisio, C., Lab. Investig., 1999, vol. 79, pp. 1327–1333.
Ambrosini, G., Adida, C., and Altieri, D.C., Nat. Med., 1997, vol. 3, pp. 917–921.
Mahotka, C., Wenzel, M., Springer, E., Gabbert, H.E., and Gerharz, C.D., Cancer Res., 1999, vol. 59, pp. 6097–6102.
Adida, C., Haioun, C., Gaulard, P., Lepage, E., Morel, P., Briere, J., Dombret, H., Reyes, F., Diebold, J., Gisselbrecht, C., Salles, G., Altieri, D.C., and Molina, T.J., Blood, 2000, vol. 96, pp. 1921–1925.
Kawasaki, H., Altieri, D.C., Lu, C.D., Toyoda, M., Tenjo, T., and Tanigawa, N., Cancer Res., 1998, vol. 58, pp. 5071–5074.
Lu, C.D., Altieri, D.C., and Tanigawa, N., Cancer Res., 1998, vol. 58, pp. 1808–1812.
Tanaka, K., Iwamoto, S., Gon, G., Nohara, T., Iwamoto, M., and Tanigawa, N., Clin. Cancer Res., 2000, vol. 6, pp. 127–134.
Satoh, K., Kaneko, K., Hirota, M., Masamune, A., Satoh, A., and Shimosegawa, T., Cancer, 2001, vol. 92, pp. 271–278.
Tsuruma, T., Hata, F., Torigoe, T., Furuhata, T., Idenoue, S., Kurotaki, T., Yamamoto, M., Yagihashi, A., et al., J. Transl. Med., 2004, vol. 2, p. 19.
Wobser, M., Keikavoussi, P., Kunzmann, V., Weininger, M., Andersen, M.H., and Becker, J.C., Cancer Immunol. Immunother., 2006, vol. 55, pp. 1294–1298.
Reker, S., Meier, A., Holten-Andersen, L., Svane, I.M., Becker, J.C., Straten, P., and Andersen, M.H., Cancer Biol. Ther., 2004, vol. 3, pp. 173–179.
Friedrichs, B., Siegel, S., Andersen, M.H., Schmitz, N., and Zeis, M., Leuk. Lymphoma, 2006, vol. 47, pp. 978–985.
Vambutas, A., DeVoti, J., Nouri, M., Drijfhout, J.W., Lipford, G.B., Bonagura, V.R., van der Burg, S.H., and Melief, C.J., Vaccine, 2005, vol. 23, pp. 5271–5280.
Zwaveling, S., Ferreira, Mota, S.C., Nouta, J., Johnson, M., Lipford, G.B., Offringa, R., van der Burg, S.H., and Melief, C.J., J. Immunol., 2002, vol. 169, pp. 350–358.
Vol’pina, O.M., Titova, M.A., Zhmak, M.N., Koroev, D.O., Oboznaya, M.V., Volkova, T.D., and Ivanov, V.T., Bioorg. Khim., 2002, vol. 28, pp. 387–395; Rus. J. Bioorg. Chem., 2002, vol. 28, pp. 349–356.
Vol’pina, O.M., Titova, M.A., Koroev, D.O., Volkova, T.D., Oboznaya, M.V., Zhmak, M.N., Alekseev, T.A., and Tsetlin, V.I., Bioorg. Khim., 2006, vol. 32, pp. 169–175; Rus. J. Bioorg. Chem., 2006, vol. 32, pp. 154–159.
Vol’pina, O.M., Volkova, T.D., Koroev, D.O., Ivanov, V.T., Ozherelkov, S.V., Khoretonenko, M.V., Vorovitch, M.F., Stephenson, J.R., and Timofeev, A.V., Virus Res., 2005, vol. 112, pp. 95–99.
Cribbs, D.H., Ghochikyan, A., Vasilevko, V., Tran, M., Petrushina, I., Sadzikava, N., Babikyan, D., Kesslak, P., Kieber-Emmons, T., Cotman, C.W., and Agadjanyan, M.G., Int. Immunol., 2003, vol. 15, pp. 505–514.
Knutson, K.L., Schiffman, K., and Disis, M.L., J. Clin. Invest., 2001, vol. 107, pp. 477–484.
Finkelman, F.D., Holmes, J., Katona, I.M., Urban, J.F. Jr., Beckmann, M.P., Park, L.S., Schooley, K.A., Coffman, R.L., Mosmann, T.R., and Paul, W.E., Annu. Rev. Immunol., 1990, vol. 8, pp. 303–333.
Koroev, D.O., Kotelnikova, O.V., Vol’pina, O.M., Zhmak, M.N., Kuprianova, M.A., Agafonova, S.A., Alliluev, A.P., Litvinov, I.S., Nesmeyanov, V.A., and Ivanov, V.T., Bioorg. Khim., 2000, vol. 26, pp. 323–329; Rus. J. Bioorg. Chem., 2000, vol. 26, pp. 291–296.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © T.D. Volkova, D.O. Koroev, M.A. Titova, M.B. Oboznaya, M.P. Filatova, A.A. Pankratov, N.B. Morozova, Yu.B. Zolotavkina, R.I. Yakubovskaya, O.M. Volpina, 2008, published in Bioorganicheskaya Khimiya, 2008, Vol. 34, No. 4, pp. 457–463.
Rights and permissions
About this article
Cite this article
Volkova, T.D., Koroev, D.O., Titova, M.A. et al. Antitumor immunotherapy with the use of synthetic fragments of survivin. Russ J Bioorg Chem 34, 409–414 (2008). https://doi.org/10.1134/S1068162008040031
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1068162008040031