**4. Discussion**

The use of anti-gene therapy was also effective in another AS approach, targeted toward the molecule, TGF-beta [79]. TGF-beta2 plays a role in tumor progression by regulating key mechanisms including proliferation, metastasis, and angiogenesis. The approach of AS TGF-beta using an AS oligodeoxynucleotide—compound AP 12009, has given satisfactory results [122–124]. AP-12009 treatment was well tolerated and tumor response has been observed [123]. Two patients experienced long-lasting complete tumor remission [124]. In another clinical AS TGF-beta study, a phase I clinical trial in grade IV astrocytoma (GBM) was performed using autologous tumor cells modified by a AS TGF-beta2 vector [79]. There were indications of humoral and cellular immunity induced by the vaccine [57, 79].

As far as AS TGF-beta therapy of GBM is concerned, the treatment of patients with recurrent or refractory malignant (high-grade) glioma, WHO grade III or IV has been shown to produce results, similar to results obtained with anti IGF-I treatment. The role of peripheral blood mononuclear cells in the immune antitumor response, and prolonged survival in both anti TGF beta and anti IGF-I approaches was comparatively examined. In the case of TGF-beta, it is also important to mention, that although the first successful clinical results were published in 2006–2008, the solid experimental data, using AS technology were obtained in 1994/95 [79], which means, that long periods of research on the mechanism of AS TGF-beta and AS IGF I are required before achieving significant clinical results, confirming the usefulness of gene therapy in cancer treatment [90, 122, 123, 125–130].

In AS IGF-I or AS TGF-beta approaches, immune antitumor response, mediated by TCD8 and APC cells, was signaled as a principal mechanism of AS technology inhibiting growth factors and their signaling pathway [12, 79]. These cells being involved in HS (heat shock) protein mechanism, the inhibition of HS was introduced in clinical trials as a new direction for cancer therapy [131].

More recent clinical successful strategies of gliomas treatment, generally as a combination therapy using different types of inhibitors (i.e., imatinib, gefitinib) including antibodies (i.e., avastin) targeting growth factors and their receptors [132–136], are now focusing on anti-gene strategy, especially on antisense or triple helix technologies used alone or combined also with pharmacological treatment. As far as antisense and triple helix strategies are compared, the triple helix blockade of

**65**

provided the original work is properly cited.

1 Laboratories Legrand, Bogota, Colombia

2 ICGT–International Cancer Gene Therapy, Bogota, Colombia

3 ICGT–International Cancer Gene Therapy, Paris, France

\*Address all correspondence to: genetherapy@hotmail.fr

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

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

on translation (AS) and transcription (TH) levels, respectively.

growth factor has given better results *in vitro* and *in vivo*. But combining both strategies, the final result is most effective—stopping the expression of the oncoproteins

Among the new strategies in the efforts to successfully treat GBM, the use of AS approach targeting IGF-I, TGF-beta or VEGF, their receptors and their downstream transduction signaling elements [9, 137], appears to offer a promising solution. The final result of the signal transduction pathway element inhibition is an immune response mediated *in vivo* by lymphocytes T CD8 and APC cells. Using cancer immunogene therapy of anti-gene anti IGF-I approach, the median survival of treated glioblastoma patients has reached 22–24 months. But the near future in treating this group of disorders belongs to a combination of treatment: classical surgery, radiotherapy with immunotherapy, pharmacologic therapy, growth factor inhibitors, and the use of the antisense/triple helix gene blockade approach targeting signal transduction pathway elements of cancer processes [16, 22, 23, 36, 66, 90,

*DOI: http://dx.doi.org/10.5772/intechopen.82548*

**5. Conclusion**

125, 138–147].

**Conflict of interest**

**Author details**

Jerzy Trojan1,2,3,4\*

4 INSERM, Paris, France

No conflict of interest.

*Oncoproteins Targeting: Antibodies, Antisense, Triple-helix. Case of Anti IGF-I Cancer… DOI: http://dx.doi.org/10.5772/intechopen.82548*

growth factor has given better results *in vitro* and *in vivo*. But combining both strategies, the final result is most effective—stopping the expression of the oncoproteins on translation (AS) and transcription (TH) levels, respectively.
