A Novel Approach to the Development of Anticarcinogenic Vaccines

Kemerovo State University* E-mail: apalko@ngs.ruReceived 07. 10. 2011ABSTRACT 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, fol-lowed 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.KEy WORDS benzo[a]pyrene, anticarcinogenic vaccine, immunomimetic peptide, phage display, molecular mod-elingABBREVIATIONS CBD – cellulose-binding domain; OD – optical density; BP – benzo[a]pyrene; BSA – bovine serum albumin; AB – antibody; mAB – monoclonal antibody; ELISA – enzyme-linked immunosorbent assay; PAH – polycyclic aromatic hydrocarbonINTRODuCTIONthe un Health Agency has reported that more than 8 million people die from cancer every year. this rein-forces the need to develop a novel therapeutic strategy based on antitumor vaccines. unfortunately, such vac-cines commonly target the existing disease rather than its cause.Data from the World Health Organization (WHO) in-dicate that 90% of cancer cases are a result of the action of environmental carcinogenic agents. the bulk (70–80%) of such agents is made up of chemicals, including widely circulating polycyclic aromatic hydrocarbons (PAHs). It is an easy guess to assume that the identifi-cation of carcinogenic substances and their elimination from the sphere of human activity could serve as effec-tive cancer prophylactic. However, such an approach is virtually impossible to pursue because of many factors. therefore, the creation of antitumor defense by anti-carcinogenic vaccines buttressing the immunological barrier in animals (including humans) against carcino-genic chemicals, seems necessary.chemical carcinogens are low-molecular substanc-es that cannot, in themselves, induce an immune re-sponse. In 1937, creech and Franks first synthesized conjugates of carcinogens with high-molecular carri-ers - blood serum proteins. they found that immuni-zation of these conjugates leads to synthesis of specific anticarcinogenic antibodies (ABs). At the same time, some inhibition of carcinogen-induced tumor progres-sion was noted following pre-immunization, and the idea that the approach could be applied to prevent tumor development in humans was first put forward [1].In 1981, Moolten and associates took the next step in the development of anticarcinogenic vaccines. they prepared protein conjugates with a structural analog of carcinogen, which in itself cannot induce a tumor. the pre-immunization of animals with this conjugate