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Brain and Spinal Tumors - Primary and Secondary

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of glioma; an in vitro study of

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**Chapter 11**

**Abstract**

but is also more rapid.

**1. Introduction**

Neoplastic Brain, Glioblastoma,

*Annabelle Trojan, Heliodor Kasprzak, Oscar Gutierrez,* 

IGF-I, insulin-like growth factor 1, is present in normal fetal/neonatal brain development and reappears in the mature brain participating in the development of malignant tumor, glioblastoma multiforme. Targeting the IGF-I system has emerged as a useful method to reduce glial malignant development. Downregulation in the expression of IGF-I using antigene anti-IGF-I technology (antisense, AS, and triple helix, TH) applied in glioma cell culture established from glioblastoma biopsies induces the expression of B7 and MHC-I antigens in transfected cells (immunogenicity). The transfected cancer cells, "vaccines," after subcutaneous injection, initiated an immune response mediated by T CD8+ lymphocytes, followed by tumor regression (immunotherapy). The median survival of patients treated by surgery followed by radiotherapy and immunotherapy was 21–24 months. On the other side, the experimental work has demonstrated that IGF-I AS or TH transfected tumor cells fused with activated dendritic cells, DC, showing more striking immunogenic character. Using IGF-I TH/DC "vaccination," the efficiency in suppressing rat glioma tumors is not only relatively higher than that obtained using IGF-I TH cells

*Pedro Penagos, Ignacio Briceno, Heber O. Siachoque,* 

*Donald D. Anthony, Alvaro Alvarez and Jerzy Trojan*

**Keywords:** brain neoplastic development, glioblastoma, IGF-I, antisense, triple helix, immunogene therapy, cell hybridomas, dendritic cells, CD8

There is a convergence between onto-genesis and onco-genesisgenesis and the same specific oncoproteins like alpha-fetoprotein (AFP) or growth factors, such as IGF and TGF-beta, are present in embryo/fetal tissues and in neoplastic developing tissues and particularly in the central nervous system (CNS). As far as AFP and IGF-I are considered, there is an important remarque: the first antigen is present in both neural and glial developing and cancerous cells, whereas the second one is only present in glial developing and tumoral cells. This striking difference has oriented our studies toward the most malignant brain tumor expressing IGF-I gene: glioblastoma. In this chapter, we have described our scientific approach coming from the analysis of neoplastic CNS development conducted to glioblastoma malignancy up to the establishment of immunogene therapy of this tumor: the first cancer

and Immunotherapy

## **Chapter 11**
