Date Published: , 2010
Publisher: A.I. Gordeyev
Author(s): A.N. Glushkov, S.V. Apalko, M.L. Filipenko, V.A. Matveeva, A.Yu. Bakulina, V.G. Lunin, M.V. Kostyanko.
Human exposure to chemical carcinogens is an important etiological factor in cancer diseases. In this article, we will discuss a new approach to the development of anticarcinogenic vaccines. The main task in our research was to select a benzo[a]pyrene immunomimetic peptide considered as a hapten-specific component. For this purpose, we synthesized carcinogen-protein conjugates and prepared mono- and polyclonal antibodies to benzo[a]pyrene. Phage display technology was used to select the benzo[a]pyrene immunomimetic peptide, followed by an evaluation of the immunological properties of the obtained peptide. The obtained benzo[a]pyrene immunomimetic peptide could only simulate chemical carcinogens in the frame of the pIII protein. As a result, we prepared a recombinant protein composed of the benzo[a]pyrene immunomimetic peptide and pIII-encoding sequences. Using ELISA, we demonstrated that the recombinant protein specifically interacts with the anti-benzo[a]pyrene monoclonal antibody (mAB B2). Using molecular modeling, we predicted the 3-D structure of the mAB B2 active center and analyzed the characteristics of its interaction with different polycyclic aromatic hydrocarbons, as well as with the benzo[a]pyrene immunomimetic peptide. Thus, a comprehensive analysis of the results of the obtainment of hapten-specific components of anticarcinogenic vaccines allowed us to outline a strategy for future development in this direction.
The UN Health Agency has reported that more than 8 million people die from cancer every year. This reinforces the need to develop a novel therapeutic strategy based on antitumor vaccines. Unfortunately, such vaccines commonly target the existing disease rather than its cause.
Synthesis of conjugates
Synthesis of PAH-protein conjugates for preparation and analysis of antibodies
The use of conjugates of chemical carcinogens (or their structural analogs) with macromolecular carriers as vaccines is completely unacceptable in the immune prophylaxis of malignant tumors in humans because of the risk that the vaccine itself can induce a tumor. The hybridoma technique for the production of anti-idiotypic ABs has limitations in the optimization of the immunogenic properties of target vaccines. In addition, it is complex and expensive.