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Current Medicinal Chemistry

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Review Article

Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma

Author(s): Annabelle Trojan, Yu-Chun Lone, Ignacio Briceno and Jerzy Trojan*

Volume 31, Issue 15, 2024

Published on: 28 November, 2023

Page: [1983 - 2002] Pages: 20

DOI: 10.2174/0109298673237968231106095141

Price: $65

Abstract

Objective: Vaccines for the deadliest brain tumor - glioblastoma (GBM) - are generally based on targeting growth factors or their receptors, often using antibodies. The vaccines described in the review were prepared to suppress the principal cancer growth factor - IGF-I, using anti-gene approaches either of antisense (AS) or of triple helix (TH) type. Our objective was to increase the median survival of patients treated with AS and TH cell vaccines.

Methodology: The cells were transfected in vitro by both constructed IGF-I AS and IGF-I TH expression episomal vectors; part of these cells was co-cultured with plant phytochemicals, modulating IGF-I expression. Both AS and TH approaches completely suppressed IGF-I expression and induced MHC-1 / B7 immunogenicity related to the IGF-I receptor signal.

Results: This immunogenicity proved to be stronger in IGF-I TH than in IGF-I AS-prepared cell vaccines, especially in TH / phytochemical cells. The AS and TH vaccines generated an important TCD8+ and TCD8+CD11b- immune response in treated GBM patients and increased the median survival of patients up to 17-18 months, particularly using TH vaccines; in some cases, 2- and 3-year survival was reported. These clinical results were compared with those obtained in therapies targeting other growth factors.

Conclusion: The anti-gene IGF-I vaccines continue to be applied in current GBM personalized medicine. Technical improvements in the preparation of AS and TH vaccines to increase MHC-1 and B7 immunogenicity have, in parallel, allowed to increase in the median survival of patients.

Keywords: Cancer gene therapy, glioblastoma, immuno-gene vaccine, anti-gene technology, IGF-I, signal transduction.

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