Oncoproteins Targeting: Antibodies, Antisense, Triple-helix. Case of Anti IGF-I Cancer Immunogene Therapy

Abstract

AFP and IGF-I oncoproteins were introduced as biomarkers for cancer diagnosis and targeted in cancer therapy on protein level, but also on transcription and translation levels. The protein level was targeted using an injection of antibodies or radiolabeled proteins. The transcription and translation levels were targeted by triple helix and antisense technologies, respectively. AFP was especially useful for diagnosis and therapy of liver cancer, IGF-I was applied in diagnosis and therapy of colon, prostate, liver, uterus, ovary and brain tumors. The most spectacular results were obtained with IGF-I anti-gene strategy. IGF-I antisense (AS)/triple helix (TH) gene therapy was successfully introduced in clinical trial in the USA and Europe. When using IGF-I anti-gene therapy, cancer cells provided from biopsies were transfected in vitro with IGF-I AS, IGF-I TH expression vectors. A decrease in IGF-I gene expression of 80 and 60% was demonstrated when using TH and AS technologies, respectively. These transfected cells expressing MHC-I molecules, while injected in vivo , induced immune antitumor response mediated by CD8 lymphocytes. The median survival of treated glioblastoma patients was 21–22 months. IGF-I AS/TH immunogene therapy constitutes one of the most promising approaches in cancer therapy, and more specifically when it comes to glioblastoma treatment.