Adeno-associated virus 2 mediated gene transfer of vascular endothelial growth factor Trap: a new treatment option for glioma

Abstract

Background: Adeno-associated virus 2 mediated gene transfer of vascular endothelial growth factor Trap (AAV2-VEGF-Trap) has been reported to inhibit the growth of primary tumor as well as distant metastasis in 4T1 metastatic breast cancer models. The aim of this study was to investigate the inhibiting efficacy of AAV2-VEGF-Trap for glioma. Methods: The intracranial transplanted model of glioma in rats was established. They were treated with AAV2-VEGF-Trap, bevacizumab (BEV), temozolomide (TMZ), TMZ combined with AAV2-VEGF-Trap, TMZ combined with BEV and the control group, respectively. A 7.0 Tesla magnetic resonance (MR) was used to assess the tumor volumes and obtain the apparent diffusion coefficient (ADC) values. Immunohistochemical and terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to evaluate the effects on tumor angiogenesis, proliferation and apoptosis. Results: The combination of TMZ with AAV2-VEGF-Trap or BEV showed greater tumor growth inhibition than the other groups, and the ADC values in these two groups were larger than that of the control group. The decreased microvessel density in treatment groups which contain AAV2-VEGF-Trap or BEV was observed. The reduced proliferation activity in groups containing TMZ and increased apoptotic tumor cells in TMZ combined with AAV2-VEGF-Trap group and TMZ combined with BEV group were detected. In addition, there were no differences in antitumor effect, ADC values, Ki-67 and CD31 staining and apoptosis analysis between the two combined therapy groups. Conclusion: AAV2-VEGF-Trap has an obvious anti-angiogenic effect and inhibits the growth of glioma just by a single intravenous injection, which is similar to BEV. Moreover, there is a synergistic antitumor effect between AAV2-VEGF-Trap and TMZ.

Towards Clinical Implementation of Adeno-Associated Virus (AAV) Vectors for Cancer Gene Therapy: Current Status and Future Perspectives

“…Moreover, the same approach was used in a rat GBM model in combination with temozolomide, a chemotherapeutic drug widely used for GBM treatment. Again, a single tail vein injection of AAV2-VEGF-Trap [ 162 ] resulted in long-term expression and synergistic growth inhibitory effects were seen in combination with chemotherapy. Finally, anti-angiogenic effects were monitored by Magnetic Resonance Imaging (MRI) [ 162 ].…”

“…Again, a single tail vein injection of AAV2-VEGF-Trap [ 162 ] resulted in long-term expression and synergistic growth inhibitory effects were seen in combination with chemotherapy. Finally, anti-angiogenic effects were monitored by Magnetic Resonance Imaging (MRI) [ 162 ]. A similar approach was performed in a triple negative breast cancer model (MDA-MB-231).…”

AAV-Vectored Expression of the Vascular Normalizing Agents 3TSR and Fc3TSR, and the Anti-Angiogenic Bevacizumab Extends Survival in a Murine Model of End-Stage Epithelial Ovarian Carcinoma

“…Adeno-associated virus (AAV) gene therapy vectors are safe [ 31 ] and effective in vivo gene delivery vehicles that promote long-term transgene expression [ 32 , 33 ], with applications to cancer treatment [ 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. AAV has been used to express a wide array of anti-cancer agents including endostatin [ 41 , 42 ], angiostatin [ 43 , 44 ], pigment epithelium-derived factor (PEDF) [ 45 ], and VEGF-Trap [ 46 , 47 ], to name a few. Results from these and other studies indicate that systemic expression of antiangiogenic agents from AAV represents a potentially effective cancer treatment [ 48 ], either alone or in combination with other therapies such as chemotherapeutic drugs [ 18 , 49 ].…”

Study of diffusion‐weighted magnetic resonance imaging in the evaluation of the response to AAV2‐VEGF‐Trap neoadjuvant treatment in a triple‐negative breast cancer animal model

“…9 Animal studies have demonstrated that the growth of breast cancer and glioma can be inhibited by a single injection of AAV2-VEGF-Trap. 9,10 In this report, we aimed to evaluate the antitumor efficacy of AAV2-VEGF-Trap alone or combination with paclitaxel in a TNBC animal model.…”

“…Gene therapy using adeno‐associated virus 2 (AAV2) to deliver VEGF‐Trap achieved long‐term expression of VEGF‐Trap in vitro and in vivo . Animal studies have demonstrated that the growth of breast cancer and glioma can be inhibited by a single injection of AAV2‐VEGF‐Trap . In this report, we aimed to evaluate the antitumor efficacy of AAV2‐VEGF‐Trap alone or combination with paclitaxel in a TNBC animal model.…”