Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models

Abstract

Objectives To explore the potential benefits of combining AdGlipr1 (or AdGLIPR1) gene therapy with radiotherapy using subcutaneous prostate and bladder cancer models. Materials and methods Combination adenoviral vector-mediated gene therapy and radiotherapy were applied to 178-2 BMA and TSU-Pr1 cells in vitro and colony formation and apoptosis were analyzed. Also, combination therapies were administered to mice bearing subcutaneous 178-2 BMA and TSU-Pr1 tumors and tumor growth suppression and survival extension were compared with the monotherapies (AdGlipr1/ AdGLIPR1, radiotherapy) or control vector Adv/CMV/βgal as well as comparing single cycle treatment with two cycle treatment. Results Combination treatment significantly suppressed colony formation and increased apoptosis in vitro. In vivo, combination therapy produced significant 178-2 BMA and TSU-Pr1 tumor growth suppression and survival extension compared with the monotherapies or the control. Further tumor growth suppression and survival extension were observed after two cycles of the combination treatment. Conclusions Combining AdGlipr1 (AdGLIPR1) with radiotherapy may achieve additive or synergistic tumor control in selected prostate and bladder tumors, and additional therapeutic effects may result with repeated treatment cycle.

Combining radiotherapy and immunotherapy for prostate cancer: two decades of research from preclinical to clinical trials

“…This report reviews the interactions between tumors and the immune system as well as the immunological and abscopal effects of ionizing radiation. Our group and others have shown that different immunotherapeutic strategies Ying Huang and Wei Chen contributed equally to this work combined with radiotherapy can significantly contribute to an effective antitumor immune response (IR) [14][15][16][17][18][19]. Furthermore, to illustrate this partnership between radiation and immunotherapy, we will discuss as examples our and other investigators' experience in preclinical and clinical studies and the molecular mechanisms identified [20][21][22][23][24][25].…”

“…In situ gene therapy has been shown to have systemic effects, likely through an immunological response. We then combined this in situ gene therapy with radiotherapy, and demonstrated that the combined group showed the most significant inhibition of tumor growth and prolongation of survival compared with either therapy alone and controls [14,17,18]. The combined therapy group also had a significantly greater frequency of infiltrating CD4 T cells than the other groups.…”

“…We have also explored the benefits of combining adenoviral glioma pathogenesis-related protein 1 (AdGLIPR1) gene therapy with radiotherapy in the prostate cancer model [18]. The result demonstrated that the combined group significantly suppressed colony formation and increased apoptosis in vitro.…”

“…On the basis of our previous preclinical studies of HSV-tk gene therapy, as well as the preclinical data on combined RT-gene therapy, we designed a phase I-II study to evaluate this combined approach in the treatment of prostate cancer [14,17,18]. The results have demonstrated the safety of combining RT and gene therapy (ADV/HSV-tk gene/valacyclovir) in prostate cancer [21].…”

Use of miRNA as a Biomarker in Prostate Cancer and New Approaches

“…[119] Adenoviral Vector-mediated Gene Therapy Some other studies observed the effects of adenoviral vector-mediated gene therapy followed by radiotherapy, which was applied to 178-2 BMA and TSUPr1 cells in vitro to observe the colony formation of cells and their apoptosis process which led to tumor control with higher efficiency. [120] Arafat et al experimented the same combined (adenovirus and radiotherapy) or sole effect of using other types of adenoviruses as a vector (TRA-8 or Ad TRAIL (adenoviral encoding TRAIL)) in Human PC cell lines (LNCaP, PC-3 and DU-145) in vitro and colony-forming assay and RT-PCR were employed to determine cells' growth and genetic changes. In addition to in vitro studies, in vivo study using murine injected subcutaneously with PC cells was carried out which presented higher efficiency and lower cancer cell survival in combination therapy (vector combined with radiotherapy) rather than single treatment only Evaluated by elevation of BAX protein (responsible for apoptosis) and eventually apoptosis of cancer cells.…”