Gene Therapy of Brain, Liver and Colon Malignancies Using Anti-Gene IGF-I Approach | Chapter 5 | Medicine and Medical Research: New Perspectives Vol. 6

Aims: The oncoproteins, insulin-like growth factor type I (IGF-I) is present in normal fetal/neonatal development, absent from mature tissues, and it reappears in the development of malignant tumors. This study aims to evaluate the efficacy of targeting IGF-I in reducing brain tumor (glioblastoma), liver (hepatocarcinoma), and colon (adenocarcinoma) using a cancer gene therapy approach.

 

Background: IGF-I is involved in the development of all three embryonic derivatives but especially in normal and neoplastic neurogenesis and glial differentiation with a predominant role compared to other growth factors.

 

Methodology: When human tumor cells derived from brain glioblastoma, and comparatively studied primary hepatocarcinoma and colon adenocarcinoma are transfected in vitro with vectors expressing either IGF-I antisense RNA or inducing IGF RNA-DNA triple helix, the synthesis of IGF-I is stopped on translation or transcription levels, respectively (anti – gene strategy). Three cancer groups of two patients each, cancer stage I, after surgery and radiotherapy, were injected using anti–gene IGF-I transfected cells (’vaccines’). In the pilot clinical essay of glioblastoma treatment, the vaccines of anti-IGF-I/phytochemical type were applied.

 

Results: Down regulation in the expression of IGF-I coincides with the reappearance of B7 and MHC class I antigens at the surface of transfected cells (immunogenicity). When injected subcutaneously, the ‘vaccines’ initiate an immune reaction involving CD8+ lymphocytes, followed by tumor regression. The median survival of treated glioblastoma patients was 19 months, and even 21 months applying anti-gen/phytochemical vaccines (an average of 15 months, using chemotherapy). Using the same strategy, the patients with liver carcinoma and colon adenocarcinoma were comparatively treated; the obtained immune anti-tumor response mediated by TCD8 was like that of glioblastoma patients.

 

Conclusion: Cancer gene therapy (immuno-gene therapy of anti-gene IGF-I approach) constitutes one of the current efficient therapies for glioblastoma and other malignancies expressing IGF-I. The clinical observations should be considered as personal medicine treatment due to the personal preparation of vaccines, and moreover, the anti-gene therapy is associated with a marked personal tendency to increase CD8 immune anti-tumor response followed by an increase in median survival.

 

Author (s) Details

 

Jerzy Trojan
CEDEA / ICGT – Oncological & Autoimmune Diseases Center, Bogota D.C., Colombia, INSERM, Paris Saclay University, Villejuif, France and Collegium Medicum, Jagiellonian University, Cracow, Poland.

 

Maryam Raja
CEDEA / ICGT – Oncological & Autoimmune Diseases Center, Bogota D.C., Colombia and Department of Biotechnology, Isfahan University, Isfahan, Iran.

 

Gabriela Quintero
CEDEA / ICGT – Oncological & Autoimmune Diseases Center, Bogota D.C., Colombia and Faculty of Medicine, UNAB University, Flioridablanca, Colombia.

 

Alvaro Alvarez
Faculty of Medicine, University of Cartagena, Cartagena de Indias, Colombia.

 

Heber O. Siachoque
CEDEA / ICGT – Oncological & Autoimmune Diseases Center, Bogota D.C., Colombia.

 

Yu-Chun Lone
CEDEA / ICGT – Oncological & Autoimmune Diseases Center, Bogota D.C., Colombia and INSERM, Paris Saclay University, Villejuif, France.

 

Ignacio Bricen
CEDEA / ICGT – Oncological & Autoimmune Diseases Center, Bogota D.C., Colombia and Faculty of Medicine, La Sabana University, Bogota DC / Chia, Colombia.

 

Annabelle Trojan
Faculty of Medicine, University of Cartagena, Cartagena de Indias, Colombia.

 

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