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Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Effective antitumor immunity against murine gliomas using dendritic cells transduced with hTERTC27
Han-Xian Gong1, Lei He, Xiang-Pen Li
1Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.
Abstract:
hTERTC27, a 27-kDa hTERT C-terminal polypeptide has been demonstrated to cause hTERT-positive HeLa cell apoptosis and inhibits the growth of mouse melanoma. hTERTC27 has been associated with telomere dysfunction, regulation of gene-regulated apoptosis, the cell cycle and activation of natural killer (NK) cells, but its mechanism of action is not fully understood. Here, we report that dendritic cells (DCs) transduced with hTERTC27 can increase T-cell proliferation, and augment the concentration of interleukin-2 (IL-2) and interferon-γ (IFN-γ) in the supernatants of T cells. It can also induce antigen-specific cytotoxic T lymphocytes (CTL) against glioma cells in vitro. Moreover, hTERTC27 gene-transduced DCs exhibit a very potent cytotoxicity to glioma cells in vivo. It could prolong the survival time and inhibit the growth of glioma-bearing mice. These data suggest that hTERTC27 gene-transduced DCs can efficiently enhance immunity against gliomas in vitro and in vivo.
Insights
The hTERTC27 polypeptide enhances dendritic cell (DC) immunotherapy against gliomas. Gene-transduced DCs boost T-cell responses and exhibit potent anti-glioma activity in vitro and in vivo.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- The hTERTC27 polypeptide, a C-terminal fragment of human telomerase reverse transcriptase (hTERT), induces apoptosis in hTERT-positive cells and inhibits melanoma growth.
- While associated with telomere dysfunction, apoptosis, cell cycle regulation, and natural killer (NK) cell activation, hTERTC27's precise mechanism remains unclear.
- Dendritic cells (DCs) are crucial antigen-presenting cells for initiating immune responses.
Purpose of the Study:
- To investigate the potential of hTERTC27 gene-transduced dendritic cells (DCs) as an immunotherapy for glioma.
- To evaluate the effects of hTERTC27-modified DCs on T-cell responses and anti-glioma immunity.
Main Methods:
- Transduction of dendritic cells (DCs) with the hTERTC27 gene.
- Assessment of T-cell proliferation, interleukin-2 (IL-2), and interferon-γ (IFN-γ) production in vitro.
- Induction of antigen-specific cytotoxic T lymphocytes (CTLs) against glioma cells.
- Evaluation of in vivo anti-glioma efficacy in glioma-bearing mice.
Main Results:
- hTERTC27-transduced DCs significantly increased T-cell proliferation and augmented IL-2 and IFN-γ concentrations.
- These modified DCs induced potent antigen-specific cytotoxic T lymphocytes (CTLs) against glioma cells in vitro.
- hTERTC27 gene-transduced DCs demonstrated significant in vivo cytotoxicity against glioma cells, prolonging survival and inhibiting tumor growth in mice.
Conclusions:
- hTERTC27 gene-transduced DCs represent a promising strategy for enhancing anti-glioma immunity.
- This approach effectively boosts T-cell responses and mediates potent anti-glioma effects both in vitro and in vivo.
- hTERTC27 holds potential as a therapeutic agent for glioma immunotherapy.

