Figure 1.

Mechanism of anti-gene anti-IGF-I (antisense/triple helix) therapy of malignant tumours. The case of glioblastoma therapy: hypothetically, the same mechanism should exist in the treatment of other tumours expressing IGF-I. The mechanism of antisense therapy is a combination of an augmentation of the immune antitumour response and of an inhibition of signal transduction pathway that is involved in the transformed phenotype of the tumour. Tumour cells are transfected in vitro with a vector encoding IGF-I cDNA in antisense orientation, or with a vector inducing a formation of triple helix IGF-I structure. The transfected tumor glial cells, in absence of IGF-I, become immunogenic-expressing MHC-I and B7 molecules, and apoptotic as follows. The expression of MHC-I is due to the presence of TAP1; the expression of B7 is related directly with signal transduction pathway: TK/IRS/PI3K/PKC; the phenomenon of apoptosis is also related with signal transduction pathway: TK/IRS/PI3K/AKT/Bcl2 [4, 13–18]. After in vivo injection, together with the antigen presenting cells, APC, they activate the T CD8 (CD8CD28) lymphocytes inducing immune antitumour response against the malignant glioma (expressing MHC-I) [4, 15, 19–22].