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Euro Biotechnology 2016

November 07-09, 2016

Volume 6, Issue 7(Suppl)

J Biotechnol Biomater

ISSN: 2155-952X JBTBM, an open access journal

conferenceseries

.com

November 07-09, 2016 Alicante, Spain

12

th

Euro Biotechnology Congress

Elena Dmitriyevna Danilenko et al., J Biotechnol Biomater 2016, 6:7(Suppl)

http://dx.doi.org/10.4172/2155-952X.C1.065

The development of a novel drug on the basis of conjugates of cytokines with bisphosphonates for

the treatment of bone metastases

Elena Dmitriyevna Danilenko, G M Sysoyeva, E I Ryabchikova, A I Zakabunin, E A Volosnikova, G M Levagina and S G Gamaley

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology "Vector", Russia

T

he interest to tumor necrosis factor alpha (TNF

α

) and interferon gamma (IFNγ) as drug agents for the treatment of bone

metastases is explained by antitumor properties of these proteins as well as by their ability to regulate the remodeling

processes in bone tissue. Bisphosphonates characterized by the ability to accumulate in bone tissue and to regulate the activity

of osteoclasts/osteoblasts can be used as vector molecules for the targeted delivery of cytokines into the bone. The purpose of

this study was to develop the method for synthesizing the conjugates of TNF

α

and IFNγ with bisphosphonate alendronic acid

(ALN) and to explore their antitumor activity. The conjugates of TNF

α

or IFNγ with ALN were obtained by the synthesis on

a solid media using 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride. The method involving the fixation of

active components on a solid phase yielded conjugates of high degree homogeneity (up to 95.7%) and a stoichiometry close to

1:1. The output of conjugates in the synthesis reaction was 90±3%. In an experimental model of bone metastases of melanoma

B16-F10, induced in C57Bl/6 mice by intracardiac administration was showed that the conjugates of TNF

α

-ALN and IFNγ-

ALN had the ability to trigger necrotic changes in the tumor tissue, covering 40-90% and 30-100% of the metastasis area,

respectively. The administration of TNF

α

-ALN conjugates reduced melanoma lesions of epiphyseal and diaphyseal bone tissue

of the femur. These findings confirm the prospects of further development of a novel drug based on the conjugates of cytokines

for the treatment of bone metastases.

Biography

Elena Dmitriyevna Danilenko was graduated from Novosibirsk State University and defended her dissertation for PhD in 2006. She is currently the Director of the

Institute of Medical Biotechnology, the branch of the State Research Center of Virology and Biotechnology "Vector". She is the author of more than 50 articles in

refereed journals and 4 patents.

danilenko_ed@vector.nsc.ru