Title:Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a
Case of Glioblastoma
Volume: 31
Issue: 15
关键词:
癌症基因治疗,胶质母细胞瘤,免疫基因疫苗,抗基因技术,IGF-I,信号转导。
摘要:
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.