Ex vivo and in vivo IGF-I antisense RNA strategies for treatment of cancer in humans.

  title={Ex vivo and in vivo IGF-I antisense RNA strategies for treatment of cancer in humans.},
  author={Donald D. Anthony and Y X Pan and S G Wu and Feng Shen and Y J Guo},
  journal={Advances in experimental medicine and biology},
  • D. AnthonyY. Pan Y. Guo
  • Published 1998
  • Biology, Medicine
  • Advances in experimental medicine and biology
Two technical approaches to gene therapy for cancer utilize ex vivo and in vivo gene transfer methodology. This paper focuses on applicability and use of each of these approaches using an IGF-I antisense RNA strategy of treatment. Insulin-like growth factor I (IGF-I) and IGF-II have pivotal roles in cell proliferation and development (for review see 1–4). The preponderance of peptide synthesis and activity occur during fetal development. Protein synthesis is down-regulated in most mature… 

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

  • T. Jerzy
  • Biology, Medicine
    Antisense Therapy
  • 2019
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

IGF-I triple helix gene therapy of rat and human gliomas.

The IGF-I antigene therapy of human glioblastoma multiforme increases immune response of treated patients and may be related to both MHC-I and B7 expression in cells used for therapy.

Human glioma cells transformed by IGF-I triple helix technology show immune and apoptotic characteristics determining cell selection for gene therapy of glioblastoma

IGF-I triple helix transfected glioma cells are characterised by immune and apoptotic phenomena that appear to be related and should have the following characteristics: the absence of IGF-I, the presence of both MHC-I and B7 molecules, and signs of apoptosis.

Neoplastic Brain, Glioblastoma, and Immunotherapy

Experimental work has demonstrated that IGF-I AS or TH transfected tumor cells fused with activated dendritic cells, DC, showing more striking immunogenic character, and the efficiency in suppressing rat glioma tumors is not only relatively higher than that obtained using IGF-i TH cells but is also more rapid.

In situ expression of soluble B7-1 in the context of oncolytic herpes simplex virus induces potent antitumor immunity.

The results demonstrate that the use of soluble B7-1 for immune gene therapy is a potent and clinically applicable means of in situ cancer vaccination.

Presence of MHC-I in rat glioma cells expressing antisense IGF-I-receptor RNA.

The immunogenicity of IGF-I-R antisense glioma cells is related to MHC-I presence; therefore both approaches of antisense IGF-i and of antisensing IGF- I-R could be use in paralel for cellular therapy of glioblastoma.

Rescue of MHC-1 Antigen Processing Machinery by Down-Regulation in Expression of IGF-1 in Human Glioblastoma Cells

The simultaneous reversion in expression of the multiple constituents of MHC-1 antigen processing path and up-regulation in expression that occurs with down- regulation in IGF-1 may have a role in reinforcement of immunity against tumor antigen(s) in some animal cancers and in humans with Glioblastoma Multiforme.

Gene Therapy of Glioblastoma: Anti – Gene Anti IGF-I Strategy

This hypothesis has strongly underlined the usefulness of techniques permitting to target and stop the expression of growth factors present in tumoral development by anti – gene strategies, particularly antisense approach.



Loss of tumorigenicity of rat glioblastoma directed by episome-based antisense cDNA transcription of insulin-like growth factor I.

No infiltration of mononuclear cells was apparent in the glioma tumors resulting from injection of parental (nontransfected) cells, suggesting that the parental cells, but not the antisense IGF-I transfectants, escape the host immune response.

Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors.

The fact that the injection of C6 cells expressing an antisense RNA to IGF-1R RNA leads to regression of already established wild-type C6 tumors suggests the possibility of practical applications and demonstrates the critical importance of the IGF- 1R in glioblastoma cell growth, clonogenicity, and tumorigenicity.

Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA.

Antisense blocking of IGF-I expression may reverse a phenotype that allows C6 glioma cells to evade the immune system and cause regression of established brain glioblastomas when injected at a point distal to the tumor.

Insulin-like growth factor-I receptor. Its role in cell proliferation, apoptosis, and tumorigenicity.

  • R. RubinR. Baserga
  • Biology
    Laboratory investigation; a journal of technical methods and pathology
  • 1995
A mutational analysis of the IGF-I receptor has shown that specific domains are involved in its mitogenicity or its ability to facilitate transformation and that these two processes can be separated at the level of the receptor itself.

Gene therapy for cancer: what have we done and where are we going?

A review of clinical trial results to date indicates that these treatments can mediate tumor regression with acceptably low toxicity and important areas for future research include modifying viral vectors to reduce toxicity and immunogenicity, and increasing the transduction efficiency of nonviral vectors.

Regression of C6 rat brain tumors by cells expressing an antisense insulin-like growth factor I receptor RNA.

It is demonstrated that C6 cells expressing an antisense IGF-IR RNA implanted for 24 h in the subcutaneous tissue of the rats are able to elicit an anti-tumor response in the brain, leading to complete brain tumor regression and long-term survival of the Rats.

Insulin-like growth factors and their receptors in growth.

  • A. D'ercole
  • Biology, Medicine
    Endocrinology and metabolism clinics of North America
  • 1996

Control of insulin-like growth factor (IGF) action by regulation of IGF-I receptor expression.

Persistent receptor expression due to mutational loss of WT1 function may contribute to the etiology of Wilms tumor and decreased WT1 expression and subsequent up-regulation of the IGF-I receptor has also been implicated in non-malignant proliferative disorders such as benign prostatic hyperplasia.

Insulin-like growth factor II (IGF-II) and the IGF-II/mannose-6-phosphate receptor: the myth continues.

It is now thought that IGF-II acts as a growth factor during fetal life and development and could act as a Growth and differentiation factor in the central nervous system.

Tumor suppressor genes, growth factor genes, and oncogenes in hepatitis B virus‐associated hepatocellular carcinoma

  • E. Tabor
  • Biology, Medicine
    Journal of medical virology
  • 1994
A series of changes in the genes that control hepatocyte growth, or interference with the protein products of these genes, appears to have an important role in the etiology of hepatocellular