RESUMO
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.
RESUMO
AIM: To develop experimental model for definition of immunological images of chemical carcinogens. MATERIALS AND METHODS: The conjugates of benzo[a]pyrene, benz[a]anthracene, anthracene, chrysene and pyrene with bovine serum albumin and yeast hexokinase were synthesized. Rabbits were immunized by bovine serum albumin-hapten conjugates. Antibodies to each hapten were isolated from the serum by affinity chromatography with the hapten-yeast hexokinase-Sepharose sorbents. The binding of each hapten with each antibody was determined by competitive immunoassay. RESULTS: The immunological images of all the investigated chemical compounds were described. CONCLUSION: The model is proposed to determine the internal immunological images of anti-idiotypic monoclonal antibodies to chemical carcinogens.