DEVELOPMENT OF STRATEGIES FOR PREVENTION OF NEOPLASTIC PROCESSES ON CELLULAR AND ORGANISM LEVELS IN VITRO AND IN VIVO. A PILOT STUDY

Iskra V Sainova*, Ilina Valkova, Tzveta Markova and Elena Nikolova

ABSTRACT

Different methods for prevention of neo-plastic transformation and activation of anti-malignant properties of in vitro-cultivated cells on both cellular and organism levels for in vitro- and in vivo-applications were developed and tested. Commercial mixed recombinant DNA-constructs, based on adeno-associated virus (AAV) (Parvoviridae family) DNA-genome were designed, containing copy of oncogene and of tumor-suppressor gene, respectively. The observed signs of early myeloid and phagocytic differentiation of non-transfected normal embryonic cells, co-cultivated with different types of transfected and non-transfected cells, containing malignant antigens, was accepted as a proof for preserved normal/non-malignant characteristics of the transfected cells, containing additional oncogene copy, on the one hand, but also for a strategy for support of adequate anti-malignant immune response, on the other, mainly by the protein products of the oncogenes in their role of active antigens. As a confirmation about the anti-neoplastic activity of tumor-suppressor gene was the noticed improvement in the general blood picture of experimental Balb/c mice, inoculated with both malignant cells and transfected mESCs, containing additionally-inserted copy of this gene, in comparison with that of animals, inoculated only with malignant cells.

Keywords: Recombinant DNA-constructs, gene transfection, cell co-cultivation.