Brain stem cells and IGF-I: implications in development, regeneration and cancer therapeutics

Abstract

For the past 40 years, our challenge has been finding a solution for the treatment of brain tumors using our knowledge of the evolution of life, the chemistry of proteins, genetics, and molecular biology. Efficient strategies were established by the construction of vectors targeting oncoproteins or growth factors (i.e. IGF-I, AFP) present during the development of the embryonic and fetal nervous system tissues originating from neural stem cells. The neoplastic stem cells, PCC3 and PCC4, derived from mouse teratocarcinoma – tumor mimicking the structures of developing central nervous system were transfected with the vectors expressing either antisense IGF-I RNA or IGF-I RNA forming a triple helix RNA-DNA. Both approaches completely stopped the synthesis of the IGF-I growth factor and converted the stem cells into immunogenic cells expressing MHC-I and B7. The immunogenic anti IGF-I transfected cells became antitumor vaccines. The role played by stem cells in the nervous system has motivated us in the search for knowledge focused on self-regeneration and therapeutic strategies. The strategy of Anti IGF-I vaccines was applied with success for therapy of glioblastoma.